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Tamkin E, Lorenz BP, McCarty A, Fulte S, Eisenmesser E, Horswill AR, Clark SE. Airway Corynebacterium interfere with Streptococcus pneumoniae and Staphylococcus aureus infection and express secreted factors selectively targeting each pathogen. Infect Immun 2025; 93:e0044524. [PMID: 39705185 PMCID: PMC11834435 DOI: 10.1128/iai.00445-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/02/2024] [Indexed: 12/22/2024] Open
Abstract
The composition of the respiratory tract microbiome is a notable predictor of infection-related morbidities and mortalities among both adults and children. Species of Corynebacterium, which are largely present as commensals in the upper airway and other body sites, are associated with lower colonization rates of opportunistic bacterial pathogens such as Streptococcus pneumoniae and Staphylococcus aureus. In this study, Corynebacterium-mediated protective effects against S. pneumoniae and S. aureus were directly compared using in vivo and in vitro models. Pre-exposure to Corynebacterium pseudodiphtheriticum reduced the ability of S. aureus and S. pneumoniae to infect the lungs of mice, indicating a broadly protective effect. Adherence of both pathogens to human respiratory tract epithelial cells was significantly impaired following pre-exposure to C. pseudodiphtheriticum or Corynebacterium accolens, and this effect was dependent on live Corynebacterium colonizing the epithelial cells. However, Corynebacterium-secreted factors had distinct effects on each pathogen. Corynebacterium lipase activity was bactericidal against S. pneumoniae, but not S. aureus. Instead, the hemolytic activity of pore-forming toxins produced by S. aureus was directly blocked by a novel Corynebacterium-secreted factor with protease activity. Taken together, these results suggest diverse mechanisms by which Corynebacterium contribute to the protective effect of the airway microbiome against opportunistic bacterial pathogens.
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Affiliation(s)
- Emily Tamkin
- Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Brian P. Lorenz
- Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Arianna McCarty
- Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Sam Fulte
- Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Elan Eisenmesser
- Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Alexander R. Horswill
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Sarah E. Clark
- Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado, USA
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Zhang Y, Yuan F, Liu Z, Huang X, Hong J, Chang F, Wu D. Rare constituents of the nasal microbiome contribute to the acute exacerbation of chronic rhinosinusitis. Inflamm Res 2025; 74:14. [PMID: 39797944 DOI: 10.1007/s00011-025-01995-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/20/2024] [Accepted: 01/04/2025] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Dysbiosis of the nasal microbiome is considered to be related to the acute exacerbation of chronic rhinosinusitis (AECRS). The microbiota in the nasal cavity of AECRS patients and its association with disease severity has rarely been studied. This study aimed to characterize nasal dysbiosis in a prospective cohort of patients with AECRS. METHODS We performed a cross-sectional study of 28 patients with AECRS, 20 patients with chronic rhinosinusitis (CRS) without acute exacerbation (AE), and 29 healthy controls using 16S rRNA gene sequencing. Subjective and objective assessments of CRS disease severity during AE were also collected. RESULTS Compared to healthy controls and patients with CRS without AE, AECRS presented with a substantial decrease of the Corynebacterium_1 and a significant increase of Ralstonia and Acinetobacter at the genus level (LDA score > 2.0 [P < 0.05]). Furthermore, genera with a mean relative abundance (MRA) of less than 1% were defined as rare components based on published studies, then 29 genera with a substantial alteration in AECRS were rare constituents of the microbiome, of which 18 rare genera were highly associated with subjective and objective disease severity. Moreover, a combination of 15 genera could differentiate patients with AECRS with an area under the curve of 0.870 (95% CI = 0.784-0.955). Prediction of microbial functional pathways involved significantly enhanced lipopolysaccharide biosynthesis pathways and significantly decreased folate biosynthesis, sulfur relay system, and cysteine and methionine metabolism pathways in patients with AECRS. CONCLUSIONS The rare nasal microbiota (MRA < 1%) correlated with disease status and disease severity in patients with AECRS. The knowledge about the pattern of the nasal microbiome and its metabolomic pathway may contribute to the fundamental understanding of AECRS pathophysiology.
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Affiliation(s)
- Yunfan Zhang
- Department of Otolaryngology, Peking University Third Hospital, Haidian District, No. 49 Huayuan North Road, Beijing, 100191, People's Republic of China
- Department of Medicine, Peking University, Beijing, People's Republic of China
| | - Fan Yuan
- Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China
- Department of Otolaryngology, Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Zheng Liu
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Xiaoxi Huang
- Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Junsheng Hong
- Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Feifan Chang
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People's Republic of China
| | - Dawei Wu
- Department of Otolaryngology, Peking University Third Hospital, Haidian District, No. 49 Huayuan North Road, Beijing, 100191, People's Republic of China.
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Tran TH, F Escapa I, Roberts AQ, Gao W, Obawemimo AC, Segre JA, Kong HH, Conlan S, Kelly MS, Lemon KP. Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses. mSystems 2024; 9:e0113224. [PMID: 39508593 DOI: 10.1128/msystems.01132-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 10/03/2024] [Indexed: 11/15/2024] Open
Abstract
Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. tuberculostearicum. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the United States. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least two Corynebacterium species likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the U.S. clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches. IMPORTANCE Pangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasal Corynebacterium species, along with focused experimental validations, generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches, highlighting the importance of investigating interactions among nasal Corynebacterium species. Comparing strains from two continents, C. pseudodiphtheriticum had restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in U.S. strains. Our findings contribute to understanding the functions of Corynebacterium within human nasal microbiota and to evaluating their potential for future use as biotherapeutics.
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Affiliation(s)
- Tommy H Tran
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Isabel F Escapa
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Ari Q Roberts
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Wei Gao
- The Forsyth Institute (Microbiology), Cambridge, Massachusetts, USA
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA
| | - Abiola C Obawemimo
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Julia A Segre
- Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Heidi H Kong
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Sean Conlan
- Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Matthew S Kelly
- Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham, North Carolina, USA
| | - Katherine P Lemon
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Division of Infectious Diseases, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
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González-García S, Hamdan-Partida A, Pérez-Ramos J, Aguirre-Garrido JF, Bustos-Hamdan A, Bustos-Martínez J. Comparison of the bacterial microbiome in the pharynx and nasal cavity of persistent, intermittent carriers and non-carriers of Staphylococcus aureus. J Med Microbiol 2024; 73:001940. [PMID: 39629792 PMCID: PMC11616445 DOI: 10.1099/jmm.0.001940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/13/2024] [Indexed: 12/08/2024] Open
Abstract
Introduction. Staphylococcus aureus is a bacterium that colonizes various human sites. The pharynx has been considered as a site of little clinical relevance and little studied. Recently, it has been reported that S. aureus can colonize more the pharynx than the nose. In addition, S. aureus can persist in these sites for prolonged periods of time.Hypothesis. The composition of the pharyngeal and nasal microbiome will differ between persistent, intermittent carriers and non-carriers of S. aureus.Aim. Determine whether the pharyngeal and nasal microbiome is different between carriers and non-carriers of S. aureus.Methodology. S. aureus carriers were monitored by means of pharyngeal and nasal exudates of apparently healthy adult university students for 3 months. Samples from individuals of the same carrier type were pooled, and DNA was extracted and the 16S rRNA was sequenced. The sequences were analysed in MOTHUR v.1.48.0 software, by analysing the percentages of relative abundance in the STAMP 2.1.3 program, in addition to the predictive analysis of metabolic pathways in PICRUSt2.Results. A greater colonization of S. aureus was found in the pharynx than in the nose. The microbiomes of S. aureus carriers and non-carriers do not show significant differences. The main microbiome difference found was between pharyngeal and nasal microbiomes. No significant differences were found in the abundance of the genus Staphylococcus in pharyngeal and nasal S. aureus carriers and non-carriers. The nasal microbiome was found to have more variation compared to the pharyngeal microbiome, which appears to be more stable between individuals and pools. Predictive analysis of metabolic pathways showed a greater presence of Staphylococcus-associated pathways in the nose than in the pharynx.Conclusion. S. aureus can colonize and persist in the pharynx in equal or greater proportion than in the nose. No statistically significant differences were found in the microbiome of the pharyngeal and nasal carriers and non-carriers of S. aureus, but the pharyngeal and nasal microbiomes are different independent of the type of S. aureus carrier or non-carrier. Therefore, the microbiome apparently does not influence the persistence of S. aureus.
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Affiliation(s)
- Samuel González-García
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City, Mexico
| | - Aida Hamdan-Partida
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - Julia Pérez-Ramos
- Departamento de Sistemas Biológicos, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - José Félix Aguirre-Garrido
- Departamento de Ciencias Ambientales, UAM Lerma, Av. de las Garzas 10E, l Panteón 52005, Municipio Lerma de Villada, Estado de México, Mexico
| | - Anaíd Bustos-Hamdan
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - Jaime Bustos-Martínez
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
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Gladysheva IV, Stroganova EA, Chertkov KL, Cherkasov SV. Antimicrobial Activity of Corynebacterium amycolatum ICIS 53 and Corynebacterium amycolatum ICIS 82 Against Urogenital Isolates of Multidrug-Resistant Staphylococcus aureus. Curr Microbiol 2024; 81:426. [PMID: 39448409 DOI: 10.1007/s00284-024-03936-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/04/2024] [Indexed: 10/26/2024]
Abstract
Intermicrobial interactions play a key role in the regulation of microbial populations and the colonization of various ecological niches. In the present study, we assessed the effect of cell-free supernatants (CFSs) from the vaginal isolates Corynebacterium amycolatum ICIS 53 and Corynebacterium amycolatum ICIS 82 on urogenital test strain biofilm formation of Staphylococcus aureus. Our studies showed that the CFSs of both C. amycolatum strains significantly reduced biofilm formation and disrupted preformed S. aureus biofilms. Pretreatment with C. amycolatum ICIS 53 or C. amycolatum ICIS 82 CFSs decreased the cell surface hydrophobicity and exopolysaccharide production of all the test S. aureus isolates. The scanning electron microscopy (SEM) results showed that the CFSs of corynebacteria caused the S. aureus biofilms to be small clusters scattered across the surface, there were no fibres or adhesions between cells, and the cell membrane was not damaged. Treatment of preformed biofilms with CFSs from both C. amycolatum strains resulted in a flat, scattered, and unstructured architecture. The S. aureus cell membrane was damaged. GC‒MS analysis of the CFS of C. amycolatum ICIS 53 revealed the presence of 22 chemical compounds, including long-chain fatty alcohols, esters, fatty acids and heterocyclic pyrrolizines and pyrazoles, that, according to the literature, exhibit a wide range of biological activities. The results of the present work provide insight for the study of Corynebacterium microorganisms as a source of multifunctional bioactive compounds, which may find promising applications in the medical, biotechnological and pharmaceutical industries.
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Affiliation(s)
- Irina V Gladysheva
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia.
| | - Elena A Stroganova
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Konstantin L Chertkov
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Sergey V Cherkasov
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
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Kelly MS, Shi P, Boiditswe SC, Qin E, Steenhoff AP, Mazhani T, Patel MZ, Cunningham CK, Rawls JF, Luinstra K, Gilchrist J, Maciejewski J, Hurst JH, Seed PC, Bulir D, Smieja M. The role of the microbiota in respiratory virus-bacterial pathobiont relationships in the upper respiratory tract. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.10.22.24315478. [PMID: 39502658 PMCID: PMC11537323 DOI: 10.1101/2024.10.22.24315478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
The mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants in Botswana, we performed a detailed analysis of factors that influence the dynamics of bacterial pathobiont colonization during infancy. We quantify the extent to which viruses increase the acquisition of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. We provide evidence of cooperative interactions between these pathobionts while identifying host characteristics and environmental exposures that influence the odds of pathobiont colonization during early life. Using 16S rRNA gene sequencing, we demonstrate that respiratory viruses result in losses of putatively beneficial Corynebacterium and Streptococcus species that are associated with a lower odds of pathobiont acquisition. These findings provide novel insights into viral-bacterial relationships in the URT of direct relevance to respiratory infections and suggest that the URT bacterial microbiota is a potentially modifiable mechanism by which viruses promote bacterial respiratory infections.
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Affiliation(s)
- Matthew S. Kelly
- Botswana-University of Pennsylvania Partnership, Gaborone, Botswana
- Division of Pediatric Infectious Diseases, Duke University, Durham, North Carolina, United States
- Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States
| | - Pixu Shi
- Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States
| | | | - Emily Qin
- Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, United States
| | - Andrew P. Steenhoff
- Botswana-University of Pennsylvania Partnership, Gaborone, Botswana
- Global Health Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Division of Pediatric Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
| | - Tiny Mazhani
- University of Botswana School of Medicine, Gaborone, Botswana
| | | | - Coleen K. Cunningham
- Division of Pediatric Infectious Diseases, University of California, Irvine, Children’s Hospital of Orange County, Orange, California, United States
| | - John F. Rawls
- Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States
| | - Kathy Luinstra
- Infectious Disease Research Group, Research Institute of St. Joe’s Hamilton, Hamilton, Ontario, Canada
| | - Jodi Gilchrist
- Infectious Disease Research Group, Research Institute of St. Joe’s Hamilton, Hamilton, Ontario, Canada
| | - Julia Maciejewski
- Infectious Disease Research Group, Research Institute of St. Joe’s Hamilton, Hamilton, Ontario, Canada
| | - Jillian H. Hurst
- Division of Pediatric Infectious Diseases, Duke University, Durham, North Carolina, United States
| | - Patrick C. Seed
- Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - David Bulir
- Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
| | - Marek Smieja
- Infectious Disease Research Group, Research Institute of St. Joe’s Hamilton, Hamilton, Ontario, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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Naqvi M, Utheim TP, Charnock C. Whole genome sequencing and characterization of Corynebacterium isolated from the healthy and dry eye ocular surface. BMC Microbiol 2024; 24:368. [PMID: 39342108 PMCID: PMC11438203 DOI: 10.1186/s12866-024-03517-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND The purpose of this study was to characterize Corynebacterium isolated from the ocular surface of dry eye disease patients and healthy controls. We aimed to investigate the pathogenic potential of these isolates in relation to ocular surface health. To this end, we performed whole genome sequencing in combination with biochemical, enzymatic, and antibiotic susceptibility tests. In addition, we employed deferred growth inhibition assays to examine how Corynebacterium isolates may impact the growth of potentially competing microorganisms including the ocular pathogens Pseudomonas aeruginosa and Staphylococcus aureus, as well as other Corynebacterium present on the eye. RESULTS The 23 isolates were found to belong to 8 different species of Corynebacterium with genomes ranging from 2.12 mega base pairs in a novel Corynebacterium sp. to 2.65 mega base pairs in C. bovis. Whole genome sequencing revealed the presence of a range of antimicrobial targets present in all isolates. Pangenome analysis showed the presence of 516 core genes and that the pangenome is open. Phenotypic characterization showed variously urease, lipase, mucinase, protease and DNase activity in some isolates. Attention was particularly drawn to a potentially new or novel Corynebacterium species which had the smallest genome, and which produced a range of hydrolytic enzymes. Strikingly the isolate inhibited in vitro the growth of a range of possible pathogenic bacteria as well as other Corynebacterium isolates. The majority of Corynebacterium species included in this study did not seem to possess canonical pathogenic activity. CONCLUSIONS This study is the first reported genomic and biochemical characterization of ocular Corynebacterium. A number of potential virulence factors were identified which may have direct relevance for ocular health and contribute to the finding of our previous report on the ocular microbiome, where it was shown that DNA libraries were often dominated by members of this genus. Particularly interesting in this regard was the observation that some Corynebacterium, particularly new or novel Corynebacterium sp. can inhibit the growth of other ocular Corynebacterium as well as known pathogens of the eye.
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Affiliation(s)
- Maria Naqvi
- Department of Life Sciences and Health, Faculty of Health Sciences, Oslo Metropolitan University, Postbox 4, St. Olavs Plass, Oslo, 0130, Norway.
| | - Tor P Utheim
- Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
- Department of Ophthalmology, Oslo University Hospital, Oslo, Norway
- The Norwegian Dry Eye Clinic, Ole Vigs gate 32 E, Oslo, 0366, Norway
| | - Colin Charnock
- Department of Life Sciences and Health, Faculty of Health Sciences, Oslo Metropolitan University, Postbox 4, St. Olavs Plass, Oslo, 0130, Norway
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8
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Burford-Gorst CM, Kidd SP. Phenotypic Variation in Staphylococcus aureus during Colonisation Involves Antibiotic-Tolerant Cell Types. Antibiotics (Basel) 2024; 13:845. [PMID: 39335018 PMCID: PMC11428495 DOI: 10.3390/antibiotics13090845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 09/30/2024] Open
Abstract
Staphylococcus aureus is a bacterial species that is commonly found colonising healthy individuals but that presents a paradoxical nature: simultaneously, it can migrate within the body and cause a range of diseases. Many of these become chronic by resisting immune responses, antimicrobial treatment, and medical intervention. In part, this ability to persist can be attributed to the adoption of multiple cell types within a single cellular population. These dynamics in the S. aureus cell population could be the result of its interplay with host cells or other co-colonising bacteria-often coagulase-negative Staphylococcal (CoNS) species. Further understanding of the unique traits of S. aureus alternative cell types, the drivers for their selection or formation during disease, as well as their presence even during non-pathological colonisation could advance the development of diagnostic tools and drugs tailored to target specific cells that are eventually responsible for chronic infections.
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Affiliation(s)
- Chloe M Burford-Gorst
- Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia
- Research Centre for Infectious Diseases (RCID), The University of Adelaide, Adelaide, SA 5005, Australia
| | - Stephen P Kidd
- Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia
- Research Centre for Infectious Diseases (RCID), The University of Adelaide, Adelaide, SA 5005, Australia
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9
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Tran TH, Escapa IF, Roberts AQ, Gao W, Obawemimo AC, Segre JA, Kong HH, Conlan S, Kelly MS, Lemon KP. Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.06.05.543719. [PMID: 37333201 PMCID: PMC10274666 DOI: 10.1101/2023.06.05.543719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. tuberculostearicum. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the USA. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least two Corynebacterium species likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the USA clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches.
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Affiliation(s)
- Tommy H. Tran
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Isabel F. Escapa
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Ari Q. Roberts
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Wei Gao
- The Forsyth Institute (Microbiology), Cambridge, MA, USA
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA
| | - Abiola C. Obawemimo
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Julia A. Segre
- Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Heidi H. Kong
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Sean Conlan
- Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
| | - Matthew S. Kelly
- Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham, NC, USA
| | - Katherine P. Lemon
- Alkek Center for Metagenomics & Microbiome Research, Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, USA
- Division of Infectious Diseases, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
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10
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De La Cruz KF, Townsend EC, Alex Cheong JZ, Salamzade R, Liu A, Sandstrom S, Davila E, Huang L, Xu KH, Wu SY, Meudt JJ, Shanmuganayagam D, Gibson ALF, Kalan LR. The porcine skin microbiome exhibits broad fungal antagonism. Fungal Genet Biol 2024; 173:103898. [PMID: 38815692 PMCID: PMC11662304 DOI: 10.1016/j.fgb.2024.103898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 05/02/2024] [Accepted: 05/21/2024] [Indexed: 06/01/2024]
Abstract
The skin and its microbiome function to protect the host from pathogen colonization and environmental stressors. In this study, using the Wisconsin Miniature Swine™ model, we characterize the porcine skin fungal and bacterial microbiomes, identify bacterial isolates displaying antifungal activity, and use whole-genome sequencing to identify biosynthetic gene clusters encoding for secondary metabolites that may be responsible for the antagonistic effects on fungi. Through this comprehensive approach of paired microbiome sequencing with culturomics, we report the discovery of novel species of Corynebacterium and Rothia. Further, this study represents the first comprehensive evaluation of the porcine skin mycobiome and the evaluation of bacterial-fungal interactions on this surface. Several diverse bacterial isolates exhibit potent antifungal properties against opportunistic fungal pathogens in vitro. Genomic analysis of inhibitory species revealed a diverse repertoire of uncharacterized biosynthetic gene clusters suggesting a reservoir of novel chemical and biological diversity. Collectively, the porcine skin microbiome represents a potential unique source of novel antifungals.
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Affiliation(s)
- Karinda F De La Cruz
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Elizabeth C Townsend
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, United States; Medical Scientist Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - J Z Alex Cheong
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, United States
| | - Rauf Salamzade
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, United States
| | - Aiping Liu
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Shelby Sandstrom
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Evelin Davila
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; National Summer Undergraduate Research Project, University of Arizona, Tucson, AZ, United States
| | - Lynda Huang
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Kayla H Xu
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Sherrie Y Wu
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Jennifer J Meudt
- Department of Animal & Dairy Sciences, University of Wisconsin, Madison, WI, United States; Center for Biomedical Swine Research & Innovation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Dhanansayan Shanmuganayagam
- Department of Animal & Dairy Sciences, University of Wisconsin, Madison, WI, United States; Center for Biomedical Swine Research & Innovation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Angela L F Gibson
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Lindsay R Kalan
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada; M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada; David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada.
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11
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Ortiz Moyano R, Dentice Maidana S, Imamura Y, Elean M, Namai F, Suda Y, Nishiyama K, Melnikov V, Kitazawa H, Villena J. Antagonistic Effects of Corynebacterium pseudodiphtheriticum 090104 on Respiratory Pathogens. Microorganisms 2024; 12:1295. [PMID: 39065064 PMCID: PMC11278748 DOI: 10.3390/microorganisms12071295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/04/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024] Open
Abstract
In previous studies, it was demonstrated that Corynebacterium pseudodiphtheriticum 090104, isolated from the human nasopharynx, modulates respiratory immunity, improving protection against infections. Here, the antagonistic effect of the 090104 strain on respiratory pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, was explored. In a series of in vitro studies, the capacity of C. pseudodiphtheriticum 090104, its bacterium-like particles, and its culture supernatants to coaggregate, inhibit the growth, and change the virulent phenotype of pathogenic bacteria was evaluated. The results showed that the 090104 strain was able to exert a bacteriostatic effect on K. pneumoniae and S. pneumoniae growth. In addition, C. pseudodiphtheriticum 090104 coaggregated, inhibited biofilm formation, and induced phenotypic changes in all the respiratory pathogens evaluated. In conclusion, this work demonstrated that, in addition to its beneficial effects exerted by host-microbe interactions, C. pseudodiphtheriticum 090104 can enhance protection against respiratory pathogens through its microbe-microbe interactions. The mechanisms involved in such interactions should be evaluated in future research.
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Affiliation(s)
- Ramiro Ortiz Moyano
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán 4000, Argentina; (R.O.M.); (S.D.M.); (M.E.)
| | - Stefania Dentice Maidana
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán 4000, Argentina; (R.O.M.); (S.D.M.); (M.E.)
| | - Yoshiya Imamura
- Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (Y.I.); (F.N.); (K.N.)
- Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Mariano Elean
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán 4000, Argentina; (R.O.M.); (S.D.M.); (M.E.)
| | - Fu Namai
- Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (Y.I.); (F.N.); (K.N.)
- Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Yoshihito Suda
- Department of Food, Agriculture and Environment, Miyagi University, Sendai 980-8572, Japan;
| | - Keita Nishiyama
- Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (Y.I.); (F.N.); (K.N.)
- Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Vyacheslav Melnikov
- Gabrichevsky Research Institute for Epidemiology and Microbiology, 125212 Moscow, Russia
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (Y.I.); (F.N.); (K.N.)
- Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Julio Villena
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucumán 4000, Argentina; (R.O.M.); (S.D.M.); (M.E.)
- Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (Y.I.); (F.N.); (K.N.)
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12
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Piewngam P, Otto M. Staphylococcus aureus colonisation and strategies for decolonisation. THE LANCET. MICROBE 2024; 5:e606-e618. [PMID: 38518792 PMCID: PMC11162333 DOI: 10.1016/s2666-5247(24)00040-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 03/24/2024]
Abstract
Staphylococcus aureus is a leading cause of death by infectious diseases worldwide. Treatment of S aureus infections is difficult due to widespread antibiotic resistance, necessitating alternative approaches and measures for prevention of infection. Because S aureus infections commonly arise from asymptomatic colonisation, decolonisation is considered a key approach for their prevention. Current decolonisation procedures include antibiotic-based and antiseptic-based eradication of S aureus from the nose and skin. However, despite the widespread implementation and partial success of such measures, S aureus infection rates remain worrisome, and resistance to decolonisation agents is on the rise. In this Review we outline the epidemiology and mechanisms of S aureus colonisation, describe how colonisation underlies infection, and discuss current and novel approaches for S aureus decolonisation, with a focus on the latest findings on probiotic strategies and the intestinal S aureus colonisation site.
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Affiliation(s)
- Pipat Piewngam
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA
| | - Michael Otto
- Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
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13
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Uzunoğlu E, Kalkancı A, Kılıç E, Kızıl Y, Aydil U, Diker KS, Uslu SS. Bacterial and fungal communities in chronic rhinosinusitis with nasal polyps. PLoS One 2024; 19:e0304634. [PMID: 38820284 PMCID: PMC11142431 DOI: 10.1371/journal.pone.0304634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 05/15/2024] [Indexed: 06/02/2024] Open
Abstract
OBJECTIVE Multiple inflammatory mechanisms dynamically interact in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Disruption of the relationship between host and environmental factors on the mucosal surface leads to the development of inflammation. Microorganisms constitute the most important part of environmental factors. METHODS 28 volunteers (18 CRSwNP patients and 10 healthy individuals) were included in the study. Eight patients were recurrent nasal polyposis cases, and the remaining were primary cases. Swab samples were taken from the middle meatus under endoscopic examination from all participants. After DNA extraction, a library was created with the Swift Amplicon 16S + ITS kit and sequenced with Illumina Miseq. Sequence analysis was performed using QIIME, UNITE v8.2 database for ITS and Silva v138 for 16S rRNA. RESULTS The predominant bacteria in all groups were Firmicutes, Proteobacteria, Actinobacteria as phyla and Staphylococcus, Corynebacterium, Sphingomonas as genera. Comparison of bacterial communities of CRSwNP patients and control group highlighted Corynebacterium, as the differentiating taxa for control group and Streptococcus, Moraxella, Rothia, Micrococcus, Gemella, and Prevotella for CRSwNP patients. The predominant fungal genus in all groups was Malassezia. Staphylococcus; showed a statistically significant negative correlation with Dolosigranulum. Corynebacterium had a positive correlation with Anaerococcus, and a negative correlation with Neisseria, Prevotella, Fusobacterium and Peptostreptococcus. CONCLUSION Nasal microbiome of CRSwNP patients shows greater inter-individual variation than the control group. Corynebacterium is less abundant in patients with CRSwNP compared to the control group. Malassezia is the predominant fungus in the nasal cavity and paranasal sinuses and correlates positively with the abundance of Corynebacterium.
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Affiliation(s)
- Eray Uzunoğlu
- Department of Otorhinolaryngology, Izmir Ekol Hospital, İzmir, Turkey
| | - Ayşe Kalkancı
- Department of Medical Microbiology, Gazi University Hospital, Ankara, Turkey
| | - Esra Kılıç
- Department of Medical Microbiology, Gazi University Hospital, Ankara, Turkey
| | - Yusuf Kızıl
- Department of Otorhinolaryngology, Gazi University Hospital, Ankara, Turkey
| | - Utku Aydil
- Department of Otorhinolaryngology, Gazi University Hospital, Ankara, Turkey
| | - Kadir Serdar Diker
- Department of Microbiology, Adnan Menderes University Faculty of Veterinary Medicine, Aydin, Turkey
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14
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沈 小, 滕 支, 李 琦, 于 振. [Analysis of nasal flora composition in children with perennial allergic rhinitis]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2024; 38:127-132;139. [PMID: 38297866 PMCID: PMC11116145 DOI: 10.13201/j.issn.2096-7993.2024.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Indexed: 02/02/2024]
Abstract
Objective:This paper focuses on the diversity of nasal microbiota in children with perennial allergic rhinitis and the differences in species composition, which may be used in the future as a biomarker for disease progression and treatment. Methods:A total of 65 subjects were enrolled, including 35 perennial AR patients（AR group） and a Control group（CG group） of 30 children without AR. Collect basic information and examination reports of nasal swabs. 16S-rDNA high-throughput sequencing technology was used to detect the microbial sequence in nasal swabs, and the composition and difference of microbial diversity in each group were analyzed by bioinformatics methods. Results:The Simpson and Shannon index of the alpha diversity in the AR group had a significantly increase compared to the CG group. Beta diversity was not different between the groups. Staphylococcus（Firmicutes） of the AR group were significantly higher than that of the CG group, but Moraxella is lower than that of the CG group. Conclusion:Nasal microbial diversity and species composition of children with allergic rhinitis differ from those of healthy children, and how the differential microorganisms interact with the host and participate in immune regulation and inflammatory response requires further study.
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Affiliation(s)
- 小飞 沈
- 南京医科大学附属儿童医院耳鼻咽喉科(南京，210008)Department of Otorhinolaryngology, the Affiliated Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - 支盼 滕
- 南京医科大学附属儿童医院耳鼻咽喉科(南京，210008)Department of Otorhinolaryngology, the Affiliated Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - 琦 李
- 南京医科大学附属儿童医院耳鼻咽喉科(南京，210008)Department of Otorhinolaryngology, the Affiliated Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - 振坤 于
- 南京医科大学附属明基医院耳鼻咽喉科Department of Otorhinolaryngology, BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University
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15
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Drigot ZG, Clark SE. Insights into the role of the respiratory tract microbiome in defense against bacterial pneumonia. Curr Opin Microbiol 2024; 77:102428. [PMID: 38277901 PMCID: PMC10922932 DOI: 10.1016/j.mib.2024.102428] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/28/2024]
Abstract
The respiratory tract microbiome (RTM) is a microbial ecosystem inhabiting different niches throughout the airway. A critical role for the RTM in dictating lung infection outcomes is underlined by recent efforts to identify community members benefiting respiratory tract health. Obligate anaerobes common in the oropharynx and lung such as Prevotella and Veillonella are associated with improved pneumonia outcomes and activate several immune defense pathways in the lower airway. Colonizers of the nasal cavity, including Corynebacterium and Dolosigranulum, directly impact the growth and virulence of lung pathogens, aligning with robust clinical correlations between their upper airway abundance and reduced respiratory tract infection risk. Here, we highlight recent work identifying respiratory tract bacteria that promote airway health and resilience against disease, with a focus on lung infections and the underlying mechanisms driving RTM-protective benefits.
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Affiliation(s)
- Zoe G Drigot
- University of Colorado School of Medicine, Department of Otolaryngology, Aurora, CO 80045, USA
| | - Sarah E Clark
- University of Colorado School of Medicine, Department of Otolaryngology, Aurora, CO 80045, USA.
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16
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Huffines JT, Boone RL, Kiedrowski MR. Temperature influences commensal-pathogen dynamics in a nasal epithelial cell co-culture model. mSphere 2024; 9:e0058923. [PMID: 38179905 PMCID: PMC10826359 DOI: 10.1128/msphere.00589-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 11/28/2023] [Indexed: 01/06/2024] Open
Abstract
Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinuses, and microbial dysbiosis associated with CRS is thought to be a key driver of host inflammation that contributes to disease progression. Staphylococcus aureus is a common upper respiratory tract (URT) pathobiont associated with higher carriage rates in CRS populations, where S. aureus-secreted toxins can be identified in CRS tissues. Although many genera of bacteria colonize the URT, few account for the majority of sequencing reads. These include S. aureus and several species belonging to the genus Corynebacterium, including Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum, which are observed at high relative abundance in the healthy URT. Studies have examined bacterial interactions between major microbionts of the URT and S. aureus, but few have done so in the context of a healthy versus diseased URT environment. Here, we examine the role of temperature in commensal, pathogen, and epithelial dynamics using an air-liquid interface cell culture model mimicking the nasal epithelial environment. Healthy URT temperatures change from the nares to the nasopharynx and are increased during disease. Temperatures representative of the healthy URT increase persistence and aggregate formation of commensal C. propinquum and C. pseudodiphtheriticum, reduce S. aureus growth, and lower epithelial cytotoxicity compared to higher temperatures correlating with the diseased CRS sinus. Dual-species colonization revealed species-specific interactions between Corynebacterium species and S. aureus dependent on temperature. Our findings suggest URT mucosal temperature plays a significant role in mediating polymicrobial and host-bacterial interactions that may exacerbate microbial dysbiosis in chronic URT diseases.IMPORTANCEChronic rhinosinusitis is a complex inflammatory disease with a significant healthcare burden. Although presence of S. aureus and microbial dysbiosis are considered mediators of inflammation in CRS, no studies have examined the influence of temperature on S. aureus interactions with the nasal epithelium and the dominant genus of the healthy URT, Corynebacterium. Interactions between Corynebacterium species and S. aureus have been documented in several studies, but none to date have examined how environmental changes in the URT may alter their interactions with the epithelium or each other. This study utilizes a polarized epithelial cell culture model at air-liquid interface to study the colonization and spatial dynamics of S. aureus and clinical isolates of Corynebacterium from people with CRS to characterize the role temperature has in single- and dual-species dynamics on the nasal epithelium.
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Affiliation(s)
- Joshua T. Huffines
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - RaNashia L. Boone
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Megan R. Kiedrowski
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA
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17
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Puls JS, Winnerling B, Power JJ, Krüger AM, Brajtenbach D, Johnson M, Bilici K, Camus L, Fließwasser T, Schneider T, Sahl HG, Ghosal D, Kubitscheck U, Heilbronner S, Grein F. Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action. THE ISME JOURNAL 2024; 18:wrae044. [PMID: 38470311 PMCID: PMC10988021 DOI: 10.1093/ismejo/wrae044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/01/2024] [Accepted: 03/11/2024] [Indexed: 03/13/2024]
Abstract
Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family of lantibiotics with an unknown ecological role and unresolved mode of action. We discovered production of an epilancin in the nasal isolate Staphylococcus epidermidis A37. Using bioinformatic tools, we found that epilancins are frequently encoded within staphylococcal genomes, highlighting their ecological relevance. We demonstrate that production of epilancin A37 contributes to Staphylococcus epidermidis competition specifically against natural corynebacterial competitors. Combining microbiological approaches with quantitative in vivo and in vitro fluorescence microscopy and cryo-electron tomography, we show that A37 enters the corynebacterial cytoplasm through a partially transmembrane-potential-driven uptake without impairing the cell membrane function. Upon intracellular aggregation, A37 induces the formation of intracellular membrane vesicles, which are heavily loaded with the compound and are essential for the antibacterial activity of the epilancin. Our work sheds light on the ecological role of epilancins for staphylococci mediated by a mode of action previously unknown for lantibiotics.
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Affiliation(s)
- Jan-Samuel Puls
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
| | - Benjamin Winnerling
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
| | - Jeffrey J Power
- Interfaculty Institute of Microbiology and Infection Medicine, Department of Infection Biology, University of Tübingen, 72076 Tübingen, Germany
| | - Annika M Krüger
- Clausius Institute of Physical and Theoretical Chemistry, University of Bonn, 53115 Bonn, Germany
| | - Dominik Brajtenbach
- Clausius Institute of Physical and Theoretical Chemistry, University of Bonn, 53115 Bonn, Germany
| | - Matthew Johnson
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia
- ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia
| | - Kevser Bilici
- Interfaculty Institute of Microbiology and Infection Medicine, Department of Infection Biology, University of Tübingen, 72076 Tübingen, Germany
| | - Laura Camus
- Interfaculty Institute of Microbiology and Infection Medicine, Department of Infection Biology, University of Tübingen, 72076 Tübingen, Germany
| | - Thomas Fließwasser
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
| | - Tanja Schneider
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
| | - Hans-Georg Sahl
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
| | - Debnath Ghosal
- Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia
- ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia
| | - Ulrich Kubitscheck
- Clausius Institute of Physical and Theoretical Chemistry, University of Bonn, 53115 Bonn, Germany
| | - Simon Heilbronner
- Interfaculty Institute of Microbiology and Infection Medicine, Department of Infection Biology, University of Tübingen, 72076 Tübingen, Germany
- German Centre for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany
- Present address: Faculty of Biology, Microbiology, Ludwig-Maximilians-University of Munich, 82152 München, Germany
| | - Fabian Grein
- Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, 53115 Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
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18
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Timme S, Wendler S, Klassert TE, Saraiva JP, da Rocha UN, Wittchen M, Schramm S, Ehricht R, Monecke S, Edel B, Rödel J, Löffler B, Ramirez MS, Slevogt H, Figge MT, Tuchscherr L. Competitive inhibition and mutualistic growth in co-infections: deciphering Staphylococcus aureus-Acinetobacter baumannii interaction dynamics. ISME COMMUNICATIONS 2024; 4:ycae077. [PMID: 38962494 PMCID: PMC11221087 DOI: 10.1093/ismeco/ycae077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 07/05/2024]
Abstract
Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and refractory to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa's capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. In addition, we observed a cross-feeding mechanism by which Sa supports the growth of Ab by providing acetoin as an alternative carbon source. This study is the first to dissect the Ab/Sa interaction dynamics wherein competitive and cooperative strategies can intertwine. Through our findings, we illuminate the ecological mechanisms supporting their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections.
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Affiliation(s)
- Sandra Timme
- Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Friedrich Schiller University Jena, Leibniz Centre for Photonics in Infection Research (LPI), D-07743 Jena, Germany
| | - Sindy Wendler
- Institute of Medical Microbiology, Jena University Hospital, D-07740 Jena, Germany
| | - Tilman E Klassert
- Respiratory Infection Dynamics, Helmholtz Centre for Infection Research – HZI, D-38124 Braunschweig, Germany
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, German Center for Lung Research (DZL), BREATH, D-30625 Hannover, Germany
| | - Joao Pedro Saraiva
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, D-04318 Leipzig, Germany
| | - Ulisses Nunes da Rocha
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, D-04318 Leipzig, Germany
| | - Manuel Wittchen
- Center for Biotechnology, Bielefeld University, D-33501 Bielefeld, Germany
| | - Sareda Schramm
- Department of Biological Science, Center for Applied Biotechnology Studies, California State University, 800 N State College Blvd, Fullerton, CA 92831, United States
| | - Ralf Ehricht
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), D-07745 Jena, Germany
- Institute of Physical Chemistry, Friedrich Schiller University Jena, Leibniz Centre for Photonics in Infection Research (LPI) , D-07743 Jena, Germany
| | - Stefan Monecke
- Leibniz Institute of Photonic Technology, Leibniz Centre for Photonics in Infection Research (LPI), D-07745 Jena, Germany
- Institute for Medical Microbiology and Virology, Dresden University Hospital, Dresden, Germany
| | - Birgit Edel
- Institute of Medical Microbiology, Jena University Hospital, D-07740 Jena, Germany
| | - Jürgen Rödel
- Institute of Medical Microbiology, Jena University Hospital, D-07740 Jena, Germany
| | - Bettina Löffler
- Institute of Medical Microbiology, Jena University Hospital, D-07740 Jena, Germany
- Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, D-07743 Jena, Germany
| | - Maria Soledad Ramirez
- Department of Biological Science, Center for Applied Biotechnology Studies, California State University, 800 N State College Blvd, Fullerton, CA 92831, United States
| | - Hortense Slevogt
- Respiratory Infection Dynamics, Helmholtz Centre for Infection Research – HZI, D-38124 Braunschweig, Germany
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, German Center for Lung Research (DZL), BREATH, D-30625 Hannover, Germany
| | - Marc Thilo Figge
- Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Friedrich Schiller University Jena, Leibniz Centre for Photonics in Infection Research (LPI), D-07743 Jena, Germany
- Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, D-07743 Jena, Germany
- Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, D-07743 Jena, Germany
| | - Lorena Tuchscherr
- Institute of Medical Microbiology, Jena University Hospital, D-07740 Jena, Germany
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19
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Roslan MAM, Omar MN, Sharif NAM, Raston NHA, Arzmi MH, Neoh HM, Ramzi AB. Recent advances in single-cell engineered live biotherapeutic products research for skin repair and disease treatment. NPJ Biofilms Microbiomes 2023; 9:95. [PMID: 38065982 PMCID: PMC10709320 DOI: 10.1038/s41522-023-00463-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 11/20/2023] [Indexed: 12/18/2023] Open
Abstract
The human microbiome has emerged as a key player in maintaining skin health, and dysbiosis has been linked to various skin disorders. Amidst growing concerns regarding the side effects of antibiotic treatments, the potential of live biotherapeutic products (LBPs) in restoring a healthy microbiome has garnered significant attention. This review aims to evaluate the current state of the art of the genetically or metabolically engineered LBPs, termed single-cell engineered LBPs (eLBPs), for skin repair and disease treatment. While some studies demonstrate promising outcomes, the translation of eLBPs into clinical applications remains a significant hurdle. Substantial concerns arise regarding the practical implementation and scalability of eLBPs, despite the evident potential they hold in targeting specific cells and delivering therapeutic agents. This review underscores the need for further research, robust clinical trials, and the exploration of current advances in eLBP-based bioengineered bacterial chassis and new outlooks to substantiate the viability and effectiveness of eLBPs as a transformative approach in skin repair and disease intervention.
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Affiliation(s)
| | - Mohd Norfikri Omar
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia
| | - Nur Azlina Mohd Sharif
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia
| | - Nurul Hanun Ahmad Raston
- Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia
| | - Mohd Hafiz Arzmi
- Department of Fundamental Dental & Medical Sciences, Kulliyyah of Dentistry, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia
- Melbourne Dental School, The University of Melbourne, 3053, Melbourne, Victoria, Australia
| | - Hui-Min Neoh
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia
| | - Ahmad Bazli Ramzi
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia.
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20
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Zhou Y, Xu X, Liu Y, Wang A, Luo Y, Liu X, Wang X, Li W, Yao X. Heterogeneous Regulation of StaphylococcusAureus by Different StaphylococcusEpidermidisagr Types in Atopic Dermatitis. J Invest Dermatol 2023; 143:2484-2493.e11. [PMID: 37271450 DOI: 10.1016/j.jid.2023.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 04/15/2023] [Accepted: 05/02/2023] [Indexed: 06/06/2023]
Abstract
The skin commensal Staphylococcus epidermidis exhibits a protective role in skin inflammation; however, the exact functions of S. epidermidis and their mechanisms in atopic dermatitis (AD) are not fully understood. Here, whole-genome sequencing was conducted on strains of S. epidermidis isolated from pediatric patients with AD and revealed significant strain-level heterogeneity in functional genes. Specific sequence analysis of S. epidermidis identified four types of accessory gene regulator (agr) according to locus variations in the agr operon, which was consistent with the metagenomic data of the contextual microbiota. The number of S. epidermidisagr type I was slightly decreased among AD isolates, whereas agr type IV was hardly detected in AD isolates. Functional experiments showed that strains of S. epidermidisagr types I and IV, but not types II and III, inhibited the expression of S. aureusagr-mediated virulence factors in vitro, suppressed S. aureus epidermal colonization, and attenuated skin inflammation in a mouse model. The delineation of genome signatures of S. epidermidis at the strain level in AD and the quorum-sensing interference between S. epidermidisagr type IV and S. aureus provide a foundation for the modulation of the skin microbiota and the treatment of AD.
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Affiliation(s)
- Yuan Zhou
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Xiaoqiang Xu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China
| | - Yang Liu
- 01 Life Institute, Shenzhen, China
| | - Ao Wang
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Yang Luo
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Xiaochun Liu
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China
| | - Xiaokai Wang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Wei Li
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China
| | - Xu Yao
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
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21
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Xiang G, Xu K, Jian Y, He L, Shen Z, Li M, Liu Q. Prolonged mask wearing changed nasal microbial characterization of young adults during the COVID-19 pandemic in Shanghai, China. Front Immunol 2023; 14:1266941. [PMID: 37908346 PMCID: PMC10614009 DOI: 10.3389/fimmu.2023.1266941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 09/18/2023] [Indexed: 11/02/2023] Open
Abstract
Background Face masks have become a common sight during the Coronavirus Disease 2019 (COVID-19) pandemic in many countries. However, the impact of prolonged face mask wearing on nasal microbiota of healthy people is not fully understood. Methods In this study, we compared the nasal microbiota of 82 young adults who wore face masks for an extended period of time to 172 mask-free peers from the same school recruited before the COVID-19 pandemic via 16S ribosomal RNA gene sequencing. Diversity, composition, and function of nasal microbiota between the two groups were analyzed. Prevalence of commensal bacteria colonized in the nasal cavity was determined by culture-based analysis. Results We observed that prolonged face mask wearers had significantly different nasal microbial characterization and metabolic function compared to mask-free controls from 2018. Specifically, the nasal microbiota of the prolonged mask wearers displayed increased abundance of Staphylococcus, Pseudoalteromonas, Corynebacterium, etc. Meanwhile, the abundance of several genera including Bacteroides, Faecalibacterium, and Agathobacter was decreased. Moreover, we observed that COVID-19 infection history did not affect the composition of nasal microbiota significantly. Additionally, the culture-based analysis revealed that Staphylococcus aureus and Corynebacterium accolens increased, and Staphylococcus epidermidis decreased in the nasal cavity of prolonged mask wearers. Conclusions Overall, our study suggests that prolonged face mask wearing can significantly alter the nasal microbiota.
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Affiliation(s)
- Guoxiu Xiang
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kai Xu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Jian
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lei He
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhen Shen
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Min Li
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Faculty of Medical Laboratory Science, College of Health Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qian Liu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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22
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Zhou Y, Liu M, Liu K, Wu G, Tan Y. Lung microbiota and potential treatment of respiratory diseases. Microb Pathog 2023:106197. [PMID: 37321423 DOI: 10.1016/j.micpath.2023.106197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/21/2023] [Accepted: 06/06/2023] [Indexed: 06/17/2023]
Abstract
The unique microbiome found in the lungs has been studied and shown to be associated with both pulmonary homeostasis and lung diseases. The lung microbiome has the potential to produce metabolites that modulate host-microbe interactions. Specifically, short-chain fatty acids (SCFAs) produced by certain strains of the lung microbiota have been shown to regulate immune function and maintain gut mucosal health. In response, this review described the distribution and composition of the microbiota in lung diseases and discussed the impact of the lung microbiota on health and lung disease. In addition, the review further elaborated on the mechanism of microbial metabolites in microbial-host interaction and their application in the treatment of lung diseases. A better understanding of the interaction between the microbiota, metabolites, and host will provide potential strategies for the development of novel methods for the treatment of pulmonary microbial induced lung diseases.
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Affiliation(s)
- Yaxuan Zhou
- Department of Psychiatry, Department of Medicine, Xiangya School of Medical, Central South University, Changsha, 410083, Hunan, China
| | - Mengjun Liu
- Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, 410083, Hunan, China
| | - Kaixuan Liu
- Department of Excellent Doctor Training, Xiangya School of Medicine, Central South University, Changsha, 410083, Hunan, China
| | - Guojun Wu
- Department of Medical Microbiology, School of Basic Medicine, Central South University, Changsha, 410083, Hunan, China.
| | - Yurong Tan
- Department of Medical Microbiology, School of Basic Medicine, Central South University, Changsha, 410083, Hunan, China.
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23
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Matijević T, Talapko J, Meštrović T, Matijević M, Erić S, Erić I, Škrlec I. Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes. World J Clin Cases 2023; 11:1669-1683. [PMID: 36970006 PMCID: PMC10037285 DOI: 10.12998/wjcc.v11.i8.1669] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 02/01/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
Diabetes mellitus, a chronic disease of metabolism, is characterized by a disordered production or cellular utilization of insulin. Diabetic foot disease, which comprises the spectrum of infection, ulceration, and gangrene, is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients. The aim of this study is to provide an evidence-based overview of diabetic foot complications. Due to neuropathy, diabetic foot infections can occur in the form of ulcers and minor skin lesions. In patients with diabetic foot ulcers, ischemia and infection are the main causes of non-healing ulcers and amputations. Hyperglycemia compromises the immune system of individuals with diabetes, leading to persistent inflammation and delayed wound healing. In addition, the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance. As a further complicating factor, the warning signs and symptoms of diabetic foot problems can easily be overlooked. Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis; accordingly, the risk of these complications in people with diabetes should be assessed annually. Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections, if peripheral arterial disease is present, revascularization should be considered to prevent limb amputation. A multidisciplinary approach to the prevention, diagnosis, and treatment of diabetic patients, including those with foot ulcers, is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.
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Affiliation(s)
- Tatjana Matijević
- Department of Dermatology and Venereology, University Hospital Center Osijek, Osijek 31000, Croatia
| | - Jasminka Talapko
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Tomislav Meštrović
- University Centre Varaždin, University North, Varaždin 42000, Croatia
- Institute for Health Metrics and Evaluation and the Department for Health Metrics Sciences, University of Washington School of Medicine, Seattle, WA 98195, United States
| | - Marijan Matijević
- Department of Surgery, National Memorial Hospital Vukovar, Vukovar 32000, Croatia
| | - Suzana Erić
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
- Department of Radiotherapy and Oncology, Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Ivan Erić
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
- Department of Surgery, Osijek University Hospital Centre, Osijek 31000, Croatia
| | - Ivana Škrlec
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
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24
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The dynamic balance of the skin microbiome across the lifespan. Biochem Soc Trans 2023; 51:71-86. [PMID: 36606709 PMCID: PMC9988004 DOI: 10.1042/bst20220216] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 01/07/2023]
Abstract
For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the lifespan. This is reflected in the dynamic shifts of the skin microbiome's diverse, inter-connected community of microorganisms with age. While there are core skin microbial taxa, the precise community composition for any individual person is determined by local skin physiology, genetics, microbe-host interactions, and microbe-microbe interactions. As a key interface with the environment, the skin surface and its appendages are also constantly exchanging microbes with close personal contacts and the environment. Hormone fluctuations and immune system maturation also drive age-dependent changes in skin physiology that support different microbial community structures over time. Here, we review recent insights into the factors that shape the skin microbiome throughout life. Collectively, the works summarized within this review highlight how, depending on where we are in lifespan, our skin supports robust microbial communities, while still maintaining microbial features unique to us. This review will also highlight how disruptions to this dynamic microbial balance can influence risk for dermatological diseases as well as impact lifelong health.
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25
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Lee SM, Keum HL, Sul WJ. Bacterial Crosstalk via Antimicrobial Peptides on the Human Skin: Therapeutics from a Sustainable Perspective. J Microbiol 2023; 61:1-11. [PMID: 36719618 DOI: 10.1007/s12275-022-00002-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 10/18/2022] [Accepted: 10/24/2022] [Indexed: 02/01/2023]
Abstract
The skin's epidermis is an essential barrier as the first guard against invading pathogens, and physical protector from external injury. The skin microbiome, which consists of numerous bacteria, fungi, viruses, and archaea on the epidermis, play a key role in skin homeostasis. Antibiotics are a fast-acting and effective treatment method, however, antibiotic use is a nuisance that can disrupt skin homeostasis by eradicating beneficial bacteria along with the intended pathogens and cause antibiotic-resistant bacteria spread. Increased numbers of antimicrobial peptides (AMPs) derived from humans and bacteria have been reported, and their roles have been well defined. Recently, modulation of the skin microbiome with AMPs rather than artificially synthesized antibiotics has attracted the attention of researchers as many antibiotic-resistant strains make treatment mediation difficult in the context of ecological problems. Herein, we discuss the overall insights into the skin microbiome, including its regulation by different AMPs, as well as their composition and role in health and disease.
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Affiliation(s)
- Seon Mi Lee
- Department of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea
| | - Hye Lim Keum
- Department of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea
| | - Woo Jun Sul
- Department of Systems Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea.
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26
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Tamai M, Yamazaki Y, Ito T, Nakagawa S, Nakamura Y. Pathogenic role of the staphylococcal accessory gene regulator quorum sensing system in atopic dermatitis. Front Cell Infect Microbiol 2023; 13:1178650. [PMID: 37124047 PMCID: PMC10140505 DOI: 10.3389/fcimb.2023.1178650] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 04/03/2023] [Indexed: 05/02/2023] Open
Abstract
The skin is home to various bacteria, archaea, fungi, and viruses, collectively referred to as the skin microbiota. Patients with certain skin diseases reportedly have unique skin "dysbiosis," a condition involving imbalanced microbiota, suggesting that dysbiosis in the skin may be either causal or a consequence of specific skin diseases. Atopic dermatitis (AD) is the most common allergic skin disease that affects 15-20% of children and 2-10% of adults worldwide. Both intrinsic genetic factors, such as susceptibility to type 2 inflammation or skin barrier dysfunction, and extrinsic environmental factors, such as air pollen and skin microbiota, contribute to AD. Staphylococcus aureus, which does not often colonize the skin of healthy individuals, is commonly identified in the lesional skin of patients with AD and is correlated with the disease flare. However, the role of S. aureus in the pathogenesis of AD has not been elucidated. Here, we discuss the pathological behavior of S. aureus, focusing on accessory gene regulator (Agr) quorum sensing, which is a fundamental bacterial cell-to-cell interaction mechanism that affects the behavior of S. aureus and other members of the microbial community. Importantly, beyond bacteria-bacteria interactions, the Agr quorum sensing system also regulates various virulence factors, which induce type 2 and IL-17-dependent skin inflammation in the host. Furthermore, the colonization of Agr-positive S. aureus in early life accelerates the development of pediatric AD. Finally, we aim to highlight the current efforts to establish novel therapeutic methods to ameliorate or prevent AD through Agr-targeted intervention.
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Affiliation(s)
- Masakazu Tamai
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuriko Yamazaki
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University, Osaka, Japan
- *Correspondence: Yuumi Nakamura, ; Yuriko Yamazaki,
| | - Tomoka Ito
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Seitaro Nakagawa
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan
- Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Yuumi Nakamura
- Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan
- Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University, Osaka, Japan
- *Correspondence: Yuumi Nakamura, ; Yuriko Yamazaki,
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27
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Chen H, Zhao Q, Zhong Q, Duan C, Krutmann J, Wang J, Xia J. Skin Microbiome, Metabolome and Skin Phenome, from the Perspectives of Skin as an Ecosystem. PHENOMICS (CHAM, SWITZERLAND) 2022; 2:363-382. [PMID: 36939800 PMCID: PMC9712873 DOI: 10.1007/s43657-022-00073-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/06/2022] [Accepted: 08/11/2022] [Indexed: 11/07/2022]
Abstract
Skin is a complex ecosystem colonized by millions of microorganisms, including bacteria, fungi, and viruses. Skin microbiota is believed to exert critical functions in maintaining host skin health. Profiling the structure of skin microbial community is the first step to overview the ecosystem. However, the community composition is highly individualized and extremely complex. To explore the fundamental factors driving the complexity of the ecosystem, namely the selection pressures, we review the present studies on skin microbiome from the perspectives of ecology. This review summarizes the following: (1) the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment, highlighting their proposed function on skin microbiota; (2) the features of dominant skin commensals to occupy ecological niches, through self-adaptation and microbe-microbe interactions; (3) how skin microbes, by their structures or bioactive molecules, reshape host skin phenotypes, including skin immunity, maintenance of skin physiology such as pH and hydration, ultraviolet (UV) protection, odor production, and wound healing. This review aims to re-examine the host-microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.
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Affiliation(s)
- Huizhen Chen
- grid.8547.e0000 0001 0125 2443Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200438 China
| | - Qi Zhao
- grid.27255.370000 0004 1761 1174Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012 China
- grid.435557.50000 0004 0518 6318IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, D-40225 Germany
| | - Qian Zhong
- grid.8547.e0000 0001 0125 2443Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200438 China
| | - Cheng Duan
- grid.8547.e0000 0001 0125 2443Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, Guangzhou, 511458 China
| | - Jean Krutmann
- grid.435557.50000 0004 0518 6318IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, D-40225 Germany
| | - Jiucun Wang
- grid.8547.e0000 0001 0125 2443Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200438 China
- grid.506261.60000 0001 0706 7839Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, 200438 China
| | - Jingjing Xia
- grid.8547.e0000 0001 0125 2443Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan University, Guangzhou, 511458 China
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28
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Altered Nasal Microbiome in Atrophic Rhinitis: A Novel Theory of Etiopathogenesis and Therapy. Microorganisms 2022; 10:microorganisms10112092. [PMID: 36363684 PMCID: PMC9694142 DOI: 10.3390/microorganisms10112092] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/28/2022] [Accepted: 09/30/2022] [Indexed: 11/05/2022] Open
Abstract
Background: Atrophic rhinitis (AtR) is a chronic nasal condition with polygenic and polybacterial etiology. We investigated the clinical outcomes of honey therapy and the associated nasal microbiome in AtR. Methods: For eight weeks, a nonrandomized control trial using a nasal spray of 10% manuka honey and saline on the right and left sides of the nose was conducted on 19 primary AtR patients. A nasal endoscopy was performed and a mucosal biopsy were taken before and after the intervention. Five of the nineteen patients were selected for microbiome and GPR43 expression studies. Results: We used manuka honey to describe an effective prebiotic treatment for atrophic rhinitis. There were nine males and ten females with an average (±SD) age of 33.8 (±10.7) years. Endoscopic scores and clinical symptoms improved in honey-treated nasal cavities (p < 0.003). There was a significant decrease in inflammation, restoration of mucus glands, and increased expression of GPR43 in the nasal cavities with honey therapy. The nasal microbiome composition before and after treatment was documented. Particularly, short chain fatty acid (SCFA) producers were positively enriched after honey therapy and correlated with improved clinical outcomes like nasal crusting, congestion, and discharge. Conclusion: Our approach to treating AtR patients with manuka honey illustrated effective clinical outcomes such as (1) decreased fetid smell, (2) thickening of the mucosa, (3) decreased inflammation with healed mucosal ulcers, (4) increased concentration of the mucosal glands, (5) altered nasal microbiome, and (6) increased expression of SCFA receptors. These changes are consequent to resetting the nasal microbiome due to honey therapy.
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29
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Barshes NR, Clark NJ, Bidare D, Dudenhoeffer JH, Mindru C, Rodriguez-Barradas MC. Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure. Open Forum Infect Dis 2022; 9:ofac475. [PMID: 36267251 PMCID: PMC9578153 DOI: 10.1093/ofid/ofac475] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 09/13/2022] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection. METHODS We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance. RESULTS In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure. CONCLUSIONS Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.
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Affiliation(s)
- Neal R Barshes
- Correspondence: Neal R. Barshes, MD, MPH, Baylor College of Medicine/Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (OCL 112), Houston, TX 77030 ()
| | - Nicholas J Clark
- School of Veterinary Science, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia
| | - Deeksha Bidare
- Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
| | - J H Dudenhoeffer
- Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA
| | - Cezarina Mindru
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Infectious Disease Section, Department of Medicine, One Baylor Plaza, Houston, Texas, USA
| | - Maria C Rodriguez-Barradas
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Infectious Disease Section, Department of Medicine, One Baylor Plaza, Houston, Texas, USA
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30
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Ma R, Hu X, Zhang X, Wang W, Sun J, Su Z, Zhu C. Strategies to prevent, curb and eliminate biofilm formation based on the characteristics of various periods in one biofilm life cycle. Front Cell Infect Microbiol 2022; 12:1003033. [PMID: 36211965 PMCID: PMC9534288 DOI: 10.3389/fcimb.2022.1003033] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 08/12/2022] [Indexed: 11/13/2022] Open
Abstract
Biofilms are colonies of bacteria embedded inside a complicated self-generating intercellular. The formation and scatter of a biofilm is an extremely complex and progressive process in constant cycles. Once formed, it can protect the inside bacteria to exist and reproduce under hostile conditions by establishing tolerance and resistance to antibiotics as well as immunological responses. In this article, we reviewed a series of innovative studies focused on inhibiting the development of biofilm and summarized a range of corresponding therapeutic methods for biological evolving stages of biofilm. Traditionally, there are four stages in the biofilm formation, while we systematize the therapeutic strategies into three main periods precisely:(i) period of preventing biofilm formation: interfering the colony effect, mass transport, chemical bonds and signaling pathway of plankton in the initial adhesion stage; (ii) period of curbing biofilm formation:targeting several pivotal molecules, for instance, polysaccharides, proteins, and extracellular DNA (eDNA) via polysaccharide hydrolases, proteases, and DNases respectively in the second stage before developing into irreversible biofilm; (iii) period of eliminating biofilm formation: applying novel multifunctional composite drugs or nanoparticle materials cooperated with ultrasonic (US), photodynamic, photothermal and even immune therapy, such as adaptive immune activated by stimulated dendritic cells (DCs), neutrophils and even immunological memory aroused by plasmocytes. The multitargeted or combinational therapies aim to prevent it from developing to the stage of maturation and dispersion and eliminate biofilms and planktonic bacteria simultaneously.
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Affiliation(s)
| | | | | | | | | | - Zheng Su
- *Correspondence: Chen Zhu, ; Zheng Su,
| | - Chen Zhu
- *Correspondence: Chen Zhu, ; Zheng Su,
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Holliday ZM, Launspach JL, Durairaj L, Singh PK, Zabner J, Stoltz DA. Effects of Tham Nasal Alkalinization on Airway Microbial Communities: A Pilot Study in Non-CF and CF Adults. Ann Otol Rhinol Laryngol 2022; 131:1013-1020. [PMID: 34674574 PMCID: PMC9021322 DOI: 10.1177/00034894211051814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES In cystic fibrosis (CF), loss of CFTR-mediated bicarbonate secretion reduces the airway surface liquid (ASL) pH causing airway host defense defects. Aerosolized sodium bicarbonate can reverse these defects, but its effects are short-lived. Aerosolized tromethamine (THAM) also raises the ASL pH but its effects are much longer lasting. In this pilot study, we tested the hypothesis that nasally administered THAM would alter the nasal bacterial composition in adults with and without CF. METHODS Subjects (n = 32 total) received intranasally administered normal saline or THAM followed by a wash out period prior to receiving the other treatment. Nasal bacterial cultures were obtained prior to and after each treatment period. RESULTS At baseline, nasal swab bacterial counts were similar between non-CF and CF subjects, but CF subjects had reduced microbial diversity. Both nasal saline and THAM were well-tolerated. In non-CF subjects, nasal airway alkalinization decreased both the total bacterial density and the gram-positive bacterial species recovered. In both non-CF and CF subjects, THAM decreased the amount of Corynebacterium accolens detected, but increased the amount of Corynebacterium pseudodiphtheriticum recovered on nasal swabs. A reduction in Staphylococcus aureus nasal colonization was also found in subjects who grew C. pseudodiphtheriticum. CONCLUSIONS This study shows that aerosolized THAM is safe and well-tolerated and that nasal airway alkalinization alters the composition of mucosal bacterial communities. CLINICAL TRIAL REGISTRATION NCT00928135 (https://clinicaltrials.gov/ct2/show/NCT00928135).
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Affiliation(s)
- Zachary M Holliday
- Department of Internal Medicine, University of Iowa, Roy J and Lucille A. Carver College of Medicine, Iowa City, IA, USA
| | - Janice L Launspach
- Department of Internal Medicine, University of Iowa, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA
| | - Lakshmi Durairaj
- Department of Internal Medicine, University of Iowa, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA
| | - Pradeep K Singh
- Departments of Microbiology and Medicine, University of Washington, Seattle, WA, USA
| | - Joseph Zabner
- Department of Internal Medicine and Pappajohn Biomedical Institute, University of Iowa, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA
| | - David A Stoltz
- Departments of Biomedical Engineering, Molecular Physiology and Biophysics, Internal Medicine and Pappajohn Biomedical Institute, University of Iowa, Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA
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32
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Microbial Interplay in Skin and Chronic Wounds. CURRENT CLINICAL MICROBIOLOGY REPORTS 2022. [DOI: 10.1007/s40588-022-00180-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Abstract
Purpose of Review
Microbial infections in chronic wounds can often lead to lower-limb amputation, decrease in quality of life, and increase in mortality rate, and there is an unmet need to distinguish between pathogens and colonisers in these chronic wounds. Hence, identifying the composition of healthy skin microbiota, microbes associated with chronic wound and healing processes, and microbial interactions and host response in healing wounds vs. non-healing wounds can help us in formulating innovative individual-centric treatment protocols.
Recent Findings
This review highlights various metabolites and biomarkers produced by microbes that have been identified to modulate these interactions, particularly those involved in host–microbe and microbe–microbe communication. Further, considering that many skin commensals demonstrate contextual pathogenicity, we provide insights into promising initiatives in the wound microbiome research.
Summary
The skin microbiome is highly diverse and variable, and considering its importance remains to be a hotspot of medical investigations and research to enable us to prevent and treat skin disorders and chronic wound infections. This is especially relevant now considering that non-healing and chronic wounds are highly prevalent, generally affecting lower extremities as seen in diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Pathogenic bacteria are purported to have a key role in deferring healing of wounds. However, the role of skin microflora in wound progression has been a subject of debate. In this review, we discuss biomarkers associated with chronic wound microenvironment along with the relevance of skin microflora and their metabolites in determining the chronicity of wounds.
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Blum FC, Whitmire JM, Bennett JW, Carey PM, Ellis MW, English CE, Law NN, Tribble DR, Millar EV, Merrell DS. Nasal microbiota evolution within the congregate setting imposed by military training. Sci Rep 2022; 12:11492. [PMID: 35798805 PMCID: PMC9263147 DOI: 10.1038/s41598-022-15059-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 06/17/2022] [Indexed: 11/26/2022] Open
Abstract
The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a ‘personalized’ approach.
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Affiliation(s)
- Faith C Blum
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Jeannette M Whitmire
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Jason W Bennett
- Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Patrick M Carey
- Benning Martin Army Community Hospital, Fort Benning, GA, USA
| | | | - Caroline E English
- Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Natasha N Law
- Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - David R Tribble
- Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Eugene V Millar
- Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.,Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - D Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
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Ortega-Peña S, Rodríguez-Martínez S, Cancino-Diaz ME, Cancino-Diaz JC. Staphylococcus epidermidis Controls Opportunistic Pathogens in the Nose, Could It Help to Regulate SARS-CoV-2 (COVID-19) Infection? Life (Basel) 2022; 12:341. [PMID: 35330092 PMCID: PMC8954679 DOI: 10.3390/life12030341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023] Open
Abstract
Staphylococcus epidermidis is more abundant in the anterior nares than internal parts of the nose, but its relative abundance changes along with age; it is more abundant in adolescents than in children and adults. Various studies have shown that S. epidermidis is the guardian of the nasal cavity because it prevents the colonization and infection of respiratory pathogens (bacteria and viruses) through the secretion of antimicrobial molecules and inhibitors of biofilm formation, occupying the space of the membrane mucosa and through the stimulation of the host's innate and adaptive immunity. There is a strong relationship between the low number of S. epidermidis in the nasal cavity and the increased risk of serious respiratory infections. The direct application of S. epidermidis into the nasal cavity could be an effective therapeutic strategy to prevent respiratory infections and to restore nasal cavity homeostasis. This review shows the mechanisms that S. epidermidis uses to eliminate respiratory pathogens from the nasal cavity, also S. epidermidis is proposed to be used as a probiotic to prevent the development of COVID-19 because S. epidermidis induces the production of interferon type I and III and decreases the expression of the entry receptors of SARS-CoV-2 (ACE2 and TMPRSS2) in the nasal epithelial cells.
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Affiliation(s)
- Silvestre Ortega-Peña
- Laboratorio Tejido Conjuntivo, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación “Luís Guillermo Ibarra Ibarra”, Ciudad de México 14389, Mexico
| | - Sandra Rodríguez-Martínez
- Laboratorio de Inmunidad Innata, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (S.R.-M.); (M.E.C.-D.)
| | - Mario E. Cancino-Diaz
- Laboratorio de Inmunidad Innata, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (S.R.-M.); (M.E.C.-D.)
| | - Juan C. Cancino-Diaz
- Laboratorio de Inmunomicrobiología, Departamento Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico
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Gladysheva IV, Cherkasov SV, Khlopko YA, Plotnikov AO. Genome Characterization and Probiotic Potential of Corynebacterium amycolatum Human Vaginal Isolates. Microorganisms 2022; 10:microorganisms10020249. [PMID: 35208706 PMCID: PMC8878833 DOI: 10.3390/microorganisms10020249] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 11/17/2022] Open
Abstract
The vaginal microbiome of healthy women contains nondiphtheria corynebacteria. The role and functions of nondiphtheria corynebacteria in the vaginal biotope are still under study. We sequenced and analysed the genomes of three vaginal C. amycolatum strains isolated from healthy women. Previous studies have shown that these strains produced metabolites that significantly increased the antagonistic activity of peroxide-producing lactic acid bacteria against pathogenic and opportunistic microorganisms and had strong antimicrobial activity against opportunistic pathogens. Analysis of the C. amycolatum genomes revealed the genes responsible for adaptation and survival in the vaginal environment, including acid and oxidative stress resistance genes. The genes responsible for the production of H2O2 and the synthesis of secondary metabolites, essential amino acids and vitamins were identified. A cluster of genes encoding the synthesis of bacteriocin was revealed in one of the annotated genomes. The obtained results allow us to consider the studied strains as potential probiotics that are capable of preventing the growth of pathogenic microorganisms and supporting colonisation resistance in the vaginal biotope.
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36
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Zhang Z, Zhang ZS, Wang X, Xi GL, Jin Z, Tang YZ. A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking. J Enzyme Inhib Med Chem 2021; 36:2087-2103. [PMID: 34823417 PMCID: PMC8635623 DOI: 10.1080/14756366.2021.1977931] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 08/31/2021] [Accepted: 09/02/2021] [Indexed: 10/29/2022] Open
Abstract
Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10-8∼5.10 × 10-5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be -12.0 kcal/mol.
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Affiliation(s)
- Zhe Zhang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Zhao-Sheng Zhang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Xiao Wang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Gao-Lei Xi
- Technology Center for China Tobacco Henan Industrial Limited Company, Zhengzhou, China
| | - Zhen Jin
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - You-Zhi Tang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
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Menberu MA, Cooksley C, Ramezanpour M, Bouras G, Wormald PJ, Psaltis AJ, Vreugde S. In vitro and in vivo evaluation of probiotic properties of Corynebacterium accolens isolated from the human nasal cavity. Microbiol Res 2021; 255:126927. [PMID: 34875424 DOI: 10.1016/j.micres.2021.126927] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/26/2021] [Accepted: 11/22/2021] [Indexed: 11/17/2022]
Abstract
Corynebacterium accolens strains are increasingly recognized as beneficial bacteria that can confer a health benefit on the host. In the current study, the probiotic potential of three C. accolens strains, C779, C781 and C787 derived from a healthy human nasal cavity were investigated. These strains were examined for their adhesion to HNECs, competition with Staphylococcus aureus for adhesion, toxicity, induction of IL-6, antibiotic susceptibility and the presence of antibiotic resistance and virulence genes. Furthermore, the safety and efficacy of strains were evaluated in vivo using Caenorhabditis elegans. The adhesion capacity of C. accolens to HNECs was strain-dependent. Highest adhesion was observed for strain C781. None of the C. accolens strains tested caused cell lysis. All strains were able to outcompete S. aureus for cell adhesion and caused a significant decrease of IL-6 production by HNECs co-exposed to S. aureus when compared to the control groups. All strains were sensitive or showed intermediate sensitivity to 10 different antibiotics. Whole Genome Sequence analysis showed C. accolens C781 and C787 did not possess antibiotic resistance genes whereas strain C779 harboured 5 genes associated with resistance to Aminoglycoside, Chloramphenicol and Erythromycin. In addition, no virulence genes were detected in any of the 3 strains. Moreover, the tested strains had no detrimental effect on worm survival and induced protection from S. aureus-mediated infection. Taken all together, C. accolens strains, C781 and C787 displayed probiotic potential and hold promise for use in clinical applications for combating dysbiosis in chronic rhinosinusitis.
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Affiliation(s)
- Martha Alemayehu Menberu
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia; Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Ethiopia
| | - Clare Cooksley
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia
| | - Mahnaz Ramezanpour
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia
| | - George Bouras
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia
| | - Peter-John Wormald
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia
| | - Alkis James Psaltis
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia
| | - Sarah Vreugde
- Department of Surgery-Otolaryngology, Head and Neck Surgery, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville, SA, Australia.
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Gladysheva IV, Chertkov KL, Cherkasov SV, Khlopko YA, Kataev VY, Valyshev AV. Probiotic Potential, Safety Properties, and Antifungal Activities of Corynebacterium amycolatum ICIS 9 and Corynebacterium amycolatum ICIS 53 Strains. Probiotics Antimicrob Proteins 2021; 15:588-600. [PMID: 34807410 DOI: 10.1007/s12602-021-09876-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2021] [Indexed: 10/19/2022]
Abstract
The purpose of this study was to evaluate the probiotic characteristics and safety and to study the antifungal activity of C. amycolatum ICIS 9 and C. amycolatum ICIS 53 against Candida spp. The probiotic potential and safety properties were assessed by standard parameters. Both strains showed good survival at pH 3 for 3 h and high tolerance to 0.3% bile salts after 4 h of incubation. The indicators of hydrophobicity, autoaggregation, and surface tension for ICIS 9 were 89.43% (n-hexane) and 73.96% (xylene) and ranged from 13.13 to 39.86% and 34.27 mN/m, respectively. For ICIS 53, they were 59.95% (n-hexane) and 45.68% (xylene), from 35.58 to 51.53% and 32.40 mN/m, respectively. The strains ICIS 9 and ICIS 53 exhibited varying levels of coaggregation with all eight examined bacterial pathogens. The ICIS 9 strain was resistant to amikacin, amoxicillin, clarithromycin, chloramphenicol, ciprofloxacin, and gentamycin. ICIS 53 was resistant only to ciprofloxacin. The cell-free supernatant of strains ICIS 9 and ICIS 53 showed good antimicrobial and antibiofilm activity against 10 pathogenic vaginal and intestinal isolates of Candida spp. The CFS of ICIS 9 was more active against intestinal isolates, and the CFS of ICIS 53 showed good antimicrobial activity against vaginal isolates while inhibiting the growth of 2 out of 5 Candida spp. isolated from the intestine. Both of the strains were capable of reducing the biofilm formation of Candida fungi. In the case of the vaginal isolates of C. krusei V1, the results showed that the inhibition levels of ICIS 9 and ICIS 53 were 36.75 and 11.4%, respectively. In the case of C. albicans (V2, V3, V7, and V8), the inhibition of biofilm formation was no more than 7.07%. ICIS 9 and ICIS 53 also significantly inhibited biofilm formation of C. krusei 2613 intestinal isolates by 42.75 and 41.87%, respectively, with ICIS 9 inhibiting biofilm formation of C. albicans (2607, 2311, 2615, and 2615) from 3.38 to 15.69% and ICIS 53 from 5.95 to 23.48%. None of the strains showed DNase, haemolytic, or gelatinase activities. The results obtained revealed that ICIS 9 and ICIS 53 have safe properties and have the potential to be developed as probiotics.
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Affiliation(s)
- I V Gladysheva
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia.
| | - K L Chertkov
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - S V Cherkasov
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - Y A Khlopko
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - V Y Kataev
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
| | - A V Valyshev
- Institute of Cellular and Intracellular Symbiosis, Ural Branch of the Russian Academy of Sciences, Orenburg, Russia
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Lunjani N, Ahearn-Ford S, Dube FS, Hlela C, O'Mahony L. Mechanisms of microbe-immune system dialogue within the skin. Genes Immun 2021; 22:276-288. [PMID: 33993202 PMCID: PMC8497273 DOI: 10.1038/s41435-021-00133-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/09/2021] [Accepted: 04/26/2021] [Indexed: 02/01/2023]
Abstract
The prevalence and severity of dermatological conditions such as atopic dermatitis have increased dramatically during recent decades. Many of the factors associated with an altered risk of developing inflammatory skin disorders have also been shown to alter the composition and diversity of non-pathogenic microbial communities that inhabit the human host. While the most densely microbial populated organ is the gut, culture and non-culture-based technologies have revealed a dynamic community of bacteria, fungi, viruses and mites that exist on healthy human skin, which change during disease. In this review, we highlight some of the recent findings on the mechanisms through which microbes interact with each other on the skin and the signalling systems that mediate communication between the immune system and skin-associated microbes. In addition, we summarize the ongoing clinical studies that are targeting the microbiome in patients with skin disorders. While significant efforts are still required to decipher the mechanisms underpinning host-microbe communication relevant to skin health, it is likely that disease-related microbial communities, or Dermatypes, will help identify personalized treatments and appropriate microbial reconstitution strategies.
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Affiliation(s)
- Nonhlanhla Lunjani
- Department of Dermatology, University of Cape Town, Cape Town, South Africa
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | | | - Felix S Dube
- Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Cape Town, South Africa
- Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Carol Hlela
- Department of Dermatology, University of Cape Town, Cape Town, South Africa
| | - Liam O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Medicine, University College Cork, Cork, Ireland.
- School of Microbiology, University College Cork, Cork, Ireland.
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40
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Gozzi-Silva SC, Teixeira FME, Duarte AJDS, Sato MN, Oliveira LDM. Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve? Front Nutr 2021; 8:674258. [PMID: 34557509 PMCID: PMC8453008 DOI: 10.3389/fnut.2021.674258] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 08/02/2021] [Indexed: 12/13/2022] Open
Abstract
Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc, selenium, iron, and magnesium), flavonoids and fatty acids, play important roles in reducing the risk of pulmonary chronic diseases and viral infections. Through their antioxidant and anti-inflammatory effects, nutrients are associated with better lung function and a lower risk of complications since they can decrease the harmful effects from the immune system during the inflammatory response. In addition, bioactive compounds can even contribute to epigenetic changes, including histone deacetylase (HDAC) modifications that inhibit the transcription of proinflammatory cytokines, which can contribute to the maintenance of homeostasis in the context of infections and chronic inflammatory diseases. These nutrients also play an important role in activating immune responses against pathogens, which can help the immune system during infections. Here, we provide an updated overview of the roles played by dietary factors and how they can affect respiratory health. Therefore, we will show the anti-inflammatory role of flavonoids, fatty acids, vitamins and microbiota, important for the control of chronic inflammatory diseases and allergies, in addition to the antiviral role of vitamins, flavonoids, and minerals during pulmonary viral infections, addressing the mechanisms involved in each function. These mechanisms are interesting in the discussion of perspectives associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its pulmonary complications since patients with severe disease have vitamins deficiency, especially vitamin D. In addition, researches with the use of flavonoids have been shown to decrease viral replication in vitro. This way, a full understanding of dietary influences can improve the lung health of patients.
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Affiliation(s)
- Sarah Cristina Gozzi-Silva
- Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, Brazil.,Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
| | - Franciane Mouradian Emidio Teixeira
- Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, Brazil.,Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
| | | | - Maria Notomi Sato
- Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, Brazil
| | - Luana de Mendonça Oliveira
- Laboratório de Dermatologia e Imunodeficiências (LIM-56), Departamento de Dermatologia, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, Brazil.,Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
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41
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Le Noci V, Bernardo G, Bianchi F, Tagliabue E, Sommariva M, Sfondrini L. Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression. Front Cell Dev Biol 2021; 9:732192. [PMID: 34604233 PMCID: PMC8485072 DOI: 10.3389/fcell.2021.732192] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/23/2021] [Indexed: 01/02/2023] Open
Abstract
The microbiota is a complex ecosystem of active microorganisms resident in the body of mammals. Although the majority of these microorganisms resides in the distal gastrointestinal tract, high-throughput DNA sequencing technology has made possible to understand that several other tissues of the human body host their own microbiota, even those once considered sterile, such as lung tissue. These bacterial communities have important functions in maintaining a healthy body state, preserving symbiosis with the host immune system, which generates protective responses against pathogens and regulatory pathways that sustain the tolerance to commensal microbes. Toll-like receptors (TLRs) are critical in sensing the microbiota, maintaining the tolerance or triggering an immune response through the direct recognition of ligands derived from commensal microbiota or pathogenic microbes. Lately, it has been highlighted that the resident microbiota influences the initiation and development of cancer and its response to therapies and that specific changes in the number and distribution of taxa correlate with the existence of cancers in various tissues. However, the knowledge of functional activity and the meaning of microbiome changes remain limited. This review summarizes the current findings on the function of TLRs as sensors of the microbiota and highlighted their modulation as a reflection of tumor-associated changes in commensal microbiota. The data available to date suggest that commensal "onco-microbes" might be able to break the tolerance of TLRs and become complicit in cancer by sustaining its growth.
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Affiliation(s)
- Valentino Le Noci
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Giancarla Bernardo
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Francesca Bianchi
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- U.O. Laboratorio di Morfologia Umana Applicata, IRCCS Policlinico San Donato, Milan, Italy
| | - Elda Tagliabue
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michele Sommariva
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Lucia Sfondrini
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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42
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Reddy K, Gericke S, Rabie H, Pienaar C, Maloba M. Exudative pharyngitis and Corynebacterium pseudodiphtheriticum: A case report and review of the literature. S Afr J Infect Dis 2021; 36:225. [PMID: 34485497 PMCID: PMC8377973 DOI: 10.4102/sajid.v36i1.225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 01/11/2021] [Indexed: 11/29/2022] Open
Abstract
Corynebacterium pseudodiphtheriticum is an established member of the normal flora of the respiratory tract. This organism is an emerging cause of respiratory tract infection, as well as infection of the skin and skin structures, urinary tract and other sterile sites. The syndrome of C. pseudodiphtheriticum exudative pharyngitis is a diagnostic challenge of particular relevance in recent times as this organism can be confused with Corynebacterium diphtheriae in the clinical setting and in the laboratory. We report a case of exudative pharyngitis, possibly due to C. pseudodiphtheriticum, in a 14-month old, incompletely vaccinated, human immunodeficiency virus (HIV)-positive infant and review the role of this organism in terms of its microbiological profile and identification, disease spectrum and antimicrobial susceptibility pattern.
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Affiliation(s)
- Kessendri Reddy
- Department of Microbiology, National Health Laboratory Services Tygerberg, Cape Town, South Africa.,Division of Medical Microbiology and Immunology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Sebastian Gericke
- Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Helena Rabie
- Division of Paediatric Infectious Diseases, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Colette Pienaar
- Department of Microbiology, National Health Laboratory Services Tygerberg, Cape Town, South Africa.,Division of Medical Microbiology and Immunology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Motlatji Maloba
- Department of Medical Microbiology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
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43
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Wolfe PN, Campfield BD, Crist BD, Keeney JA, Smith MJ, Cook JL, Stoker AM. Bacterial DNA screening to characterize surgical site infection risk in orthopaedic patients. J Orthop 2021; 27:56-62. [PMID: 34483551 DOI: 10.1016/j.jor.2021.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/22/2021] [Indexed: 10/20/2022] Open
Abstract
Purpose To provide an initial characterization of relevant bacterial DNA profiles for patients undergoing closed-fracture fixation or total joint arthroplasties. Patients and methods Swabs were collected and analyzed using Polymerase Chain Reaction from adult patients undergoing closed-fracture fixation or total shoulder, knee, or hip arthroplasties. Results Bacterial DNA profiles varied across the different orthopaedic patient populations, and produced uncharacteristic profile shifts with direct relevance to each clinical infection. Conclusion Findings provide a foundational dataset regarding bacterial colonization of relevant anatomic sites that can act as sources of surgical site infections for patients.
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Affiliation(s)
- Preston N Wolfe
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
| | - Brian D Campfield
- Geisinger Commonwealth School of Medicine, Geisinger Musculoskeletal Institute, Danville, PA, USA
| | - Brett D Crist
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
| | - James A Keeney
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
| | - Matthew J Smith
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
| | - James L Cook
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
| | - Aaron M Stoker
- University of Missouri, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA.,University of Missouri, Department of Orthopaedic Surgery, Missouri Orthopaedic Institute, 1100 Virginia Ave., Columbia, MO, 65212, USA
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Nesbitt H, Burke C, Haghi M. Manipulation of the Upper Respiratory Microbiota to Reduce Incidence and Severity of Upper Respiratory Viral Infections: A Literature Review. Front Microbiol 2021; 12:713703. [PMID: 34512591 PMCID: PMC8432964 DOI: 10.3389/fmicb.2021.713703] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 08/06/2021] [Indexed: 12/12/2022] Open
Abstract
There is a high incidence of upper respiratory viral infections in the human population, with infection severity being unique to each individual. Upper respiratory viruses have been associated previously with secondary bacterial infection, however, several cross-sectional studies analyzed in the literature indicate that an inverse relationship can also occur. Pathobiont abundance and/or bacterial dysbiosis can impair epithelial integrity and predispose an individual to viral infection. In this review we describe common commensal microorganisms that have the capacity to reduce the abundance of pathobionts and maintain bacterial symbiosis in the upper respiratory tract and discuss the potential and limitations of localized probiotic formulations of commensal bacteria to reduce the incidence and severity of viral infections.
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Affiliation(s)
- Henry Nesbitt
- Discipline of Pharmacy, Graduate School Health, University of Technology Sydney, Sydney, NSW, Australia
| | - Catherine Burke
- School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia
| | - Mehra Haghi
- Discipline of Pharmacy, Graduate School Health, University of Technology Sydney, Sydney, NSW, Australia
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Anaerobic Microbiota Derived from the Upper Airways Impact Staphylococcus aureus Physiology. Infect Immun 2021; 89:e0015321. [PMID: 34125598 DOI: 10.1128/iai.00153-21] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Staphylococcus aureus is associated with the development of persistent and severe inflammatory diseases of the upper airways. Yet, S. aureus is also carried asymptomatically in the sinonasal cavity of ∼50% of healthy adults. The causes of this duality and host and microbial factors that tip the balance between S. aureus pathogenesis and commensalism are poorly understood. We have shown that by degrading mucins, anaerobic microbiota support the growth of airway pathogens by liberating metabolites that are otherwise unavailable. Given the widely reported culture-based detection of anaerobes from individuals with chronic rhinosinusitis (CRS), here we tested our hypothesis that CRS microbiota is characterized by a mucin-degrading phenotype that alters S. aureus physiology. Using 16S rRNA gene sequencing, we indeed observed an increased prevalence and abundance of anaerobes in CRS relative to non-CRS controls. PICRUSt2-based functional predictions suggested increased mucin degradation potential among CRS microbiota that was confirmed by direct enrichment culture. Prevotella, Fusobacterium, and Streptococcus comprised a core mucin-degrading community across CRS subjects that generated a nutrient pool that augmented S. aureus growth on mucin as a carbon source. Finally, using transcriptome sequencing (RNA-seq), we observed that S. aureus transcription is profoundly altered in the presence of mucin-derived metabolites, though expression of several key metabolism- and virulence-associated pathways varied between CRS-derived bacterial communities. Together, these data support a model in which S. aureus metabolism and virulence in the upper airways are dependent upon the composition of cocolonizing microbiota and the metabolites they exchange.
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46
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Hwang J, Thompson A, Jaros J, Blackcloud P, Hsiao J, Shi VY. Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes. Exp Dermatol 2021; 30:1532-1545. [PMID: 34293242 DOI: 10.1111/exd.14435] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/18/2021] [Accepted: 07/20/2021] [Indexed: 12/22/2022]
Abstract
Atopic dermatitis (AD) is a common inflammatory dermatosis that has multiple contributing factors including genetic, immunologic and environmental. Staphylococcus aureus (SA) has long been associated with exacerbation of AD. SA produces many virulence factors that interact with the human skin and immune system. These superantigens and toxins have been shown to contribute to adhesion, inflammation and skin barrier destruction. Recent advances in genome sequencing techniques have led to a broadened understanding of the multiple ways SA interacts with the cutaneous environment in AD hosts. For example, temporal shifts in the microbiome, specifically in clonal complexes of SA, have been identified during AD flares and remission. Herein, we review mechanisms of interaction between the cutaneous microbiome and SA and highlight known differences in SA clonal complexes that contribute to AD pathogenesis. Detailed knowledge of the genetic strains of SA and cutaneous dysbiosis is becoming increasingly relevant in paving the way for microbiome-modulating and precision therapies for AD.
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Affiliation(s)
- Jonwei Hwang
- University of Illinois College of Medicine, Chicago, Illinois, USA
| | - Alyssa Thompson
- College of Medicine, University of Arizona, Tucson, Arizona, USA
| | - Joanna Jaros
- John H. Stroger Hospital Cook County Health Dermatology, Chicago, Illinois, USA
| | - Paul Blackcloud
- Division of Dermatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Jennifer Hsiao
- Division of Dermatology, University of California, Los Angeles, Los Angeles, California, USA
| | - Vivian Y Shi
- Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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The Intestinal Biofilm of Pseudomonas aeruginosa and Staphylococcus aureus Is Inhibited by Antimicrobial Peptides HBD-2 and HBD-3. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app11146595] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections.
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Weil LM, Williams MM, Shirin T, Lawrence M, Habib ZH, Aneke JS, Tondella ML, Zaki Q, Cassiday PK, Lonsway D, Farrque M, Hossen T, Feldstein LR, Cook N, Maldonado-Quiles G, Alam AN, Muraduzzaman AKM, Akram A, Conklin L, Doan S, Friedman M, Acosta AM, Hariri S, Fox LM, Tiwari TSP, Flora MS. Investigation of a Large Diphtheria Outbreak and Cocirculation of Corynebacterium pseudodiphtheriticum Among Forcibly Displaced Myanmar Nationals, 2017-2019. J Infect Dis 2021; 224:318-325. [PMID: 33245764 PMCID: PMC10846527 DOI: 10.1093/infdis/jiaa729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 11/20/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic corynebacteria (eg, Corynebacterium pseudodiphtheriticum) rarely causes diphtheria-like illness. Recently, global diphtheria outbreaks have resulted from breakdown of health care infrastructures, particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among forcibly displaced Myanmar nationals in Bangladesh. METHODS Specimens and clinical information were collected from patients presenting at diphtheria treatment centers. Swabs were tested for toxin gene (tox)-bearing C. diphtheriae by real-time polymerase chain reaction (RT-PCR) and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS Among 382 patients, 153 (40%) tested tox positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS We report confirmation of a diphtheria outbreak and identification of a cocirculating Corynebacterium species. The high proportion of C. pseudodiphtheriticum codetection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.
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Affiliation(s)
- Lauren M. Weil
- Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Margaret M. Williams
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Tahmina Shirin
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Marlon Lawrence
- Laboratory Leadership Service, Division of Scientific Education and Professional Development, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Zakir H. Habib
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Janessa S. Aneke
- IHRC Inc, Contractor to US Centers for Disease Control and Prevention, Division of Bacterial Diseases, Atlanta, Georgia, USA
| | - Maria L. Tondella
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Quazi Zaki
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Pamela K. Cassiday
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - David Lonsway
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Mirza Farrque
- Bangladesh Field Epidemiology Training Program, Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Tanvir Hossen
- Bangladesh Field Epidemiology Training Program, Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Leora R. Feldstein
- Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Nicholas Cook
- IHRC Inc, Contractor to US Centers for Disease Control and Prevention, Division of Bacterial Diseases, Atlanta, Georgia, USA
| | - Gladys Maldonado-Quiles
- IHRC Inc, Contractor to US Centers for Disease Control and Prevention, Division of Bacterial Diseases, Atlanta, Georgia, USA
| | - Ahmed N. Alam
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | | | - Arifa Akram
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
| | - Laura Conklin
- Global Immunization Division, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Stephanie Doan
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Michael Friedman
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Anna M. Acosta
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Susan Hariri
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - LeAnne M. Fox
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Tejpratap S. P. Tiwari
- Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Meerjady S. Flora
- Institute of Epidemiology, Disease Control and Research, Dhaka, Bangladesh
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Abstract
The skin microbiome is an ecosystem comprised of a multitude of microbial species interacting with their surroundings, including other microbes and host epithelial and immune cells. These interactions are the basis of important roles within the skin microbiome that provide benefit to the host, boosting multiple aspects of barrier function, a critical function of this essential organ. However, with reward always comes risk; resident skin microbes function in a context-dependent manner, set on the backdrop of a dynamic host and microbial milieu. Here, we discuss the reward of hosting a microbial ecosystem on the skin, including protection from pathogens and tuning of the skin microenvironment. We also give consideration to how these skin residents, often termed "commensals" can cause disorder, damage, and promote skin disease.
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Affiliation(s)
- Laurice Flowers
- Department of Dermatology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Elizabeth A Grice
- Department of Dermatology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
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Rhee RL, Lu J, Bittinger K, Lee JJ, Mattei LM, Sreih AG, Chou S, Miner JJ, Cohen NA, Kelly BJ, Lee H, Grayson PC, Collman RG, Merkel PA. Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis. Arthritis Rheumatol 2021; 73:1703-1712. [PMID: 33682371 DOI: 10.1002/art.41723] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 03/02/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). This study was undertaken to examine longitudinal changes in the nasal microbiome in association with relapse in GPA patients. METHODS Bacterial 16S ribosomal RNA gene sequencing was performed on nasal swabs from 19 patients with GPA who were followed up longitudinally for a total of 78 visits, including 9 patients who experienced a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models were used to evaluate the association between bacterial composition and 1) disease activity and 2) levels of antineutrophil cytoplasmic antibody (ANCA) with specificity for proteinase 3 (PR3), adjusted for medication. RESULTS Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio was observed at the visit prior to relapse, followed by a higher ratio at the time of relapse (adjusted P < 0.01). Species-level analysis identified an association between a higher abundance of nasal Corynebacterium tuberculostearicum and 1) relapse (adjusted P = 0.04) and 2) higher PR3-ANCA levels (adjusted P = 0.02). CONCLUSION In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to the onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA.
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Affiliation(s)
| | - Jiarui Lu
- University of Pennsylvania, Philadelphia
| | - Kyle Bittinger
- The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Jung-Jin Lee
- The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Lisa M Mattei
- The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | | | | | | | | | | | | | - Peter C Grayson
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
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