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Giordano L, Ware SA, Lagranha CJ, Kaufman BA. Mitochondrial DNA signals driving immune responses: Why, How, Where? Cell Commun Signal 2025; 23:192. [PMID: 40264103 PMCID: PMC12012978 DOI: 10.1186/s12964-025-02042-0] [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: 10/29/2024] [Accepted: 01/14/2025] [Indexed: 04/24/2025] Open
Abstract
There has been a recent expansion in our understanding of DNA-sensing mechanisms. Mitochondrial dysfunction, oxidative and proteostatic stresses, instability and impaired disposal of nucleoids cause the release of mitochondrial DNA (mtDNA) from the mitochondria in several human diseases, as well as in cell culture and animal models. Mitochondrial DNA mislocalized to the cytosol and/or the extracellular compartments can trigger innate immune and inflammation responses by binding DNA-sensing receptors (DSRs). Here, we define the features that make mtDNA highly immunogenic and the mechanisms of its release from the mitochondria into the cytosol and the extracellular compartments. We describe the major DSRs that bind mtDNA such as cyclic guanosine-monophosphate-adenosine-monophosphate synthase (cGAS), Z-DNA-binding protein 1 (ZBP1), NOD-, LRR-, and PYD- domain-containing protein 3 receptor (NLRP3), absent in melanoma 2 (AIM2) and toll-like receptor 9 (TLR9), and their downstream signaling cascades. We summarize the key findings, novelties, and gaps of mislocalized mtDNA as a driving signal of immune responses in vascular, metabolic, kidney, lung, and neurodegenerative diseases, as well as viral and bacterial infections. Finally, we define common strategies to induce or inhibit mtDNA release and propose challenges to advance the field.
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Affiliation(s)
- Luca Giordano
- Center for Metabolism and Mitochondrial Medicine, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
- Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
- Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Cardio-Pulmonary Institute (CPI), Justus-Liebig-University, Giessen, Germany.
| | - Sarah A Ware
- Center for Metabolism and Mitochondrial Medicine, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Claudia J Lagranha
- Center for Metabolism and Mitochondrial Medicine, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Brett A Kaufman
- Center for Metabolism and Mitochondrial Medicine, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
- Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
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Qin L, Chen Y, Luan S, Yin X, Pan J, Wang L, Yao Y, Zhou C, Bao R, Shen J, Miao Q, Hu B. Lung Microenvironment Among Patients with Nontuberculous Mycobacterial Pulmonary Disease by Metagenomic Sequencing Technique. Biomedicines 2025; 13:818. [PMID: 40299453 PMCID: PMC12025003 DOI: 10.3390/biomedicines13040818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/17/2025] [Accepted: 03/23/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an increasingly prevalent chronic infection, where the host immune status plays a crucial role in disease susceptibility and progression. The complex pulmonary microenvironment, characterized by diverse microbial communities and host immune interactions, exhibits distinct features that may be fundamentally altered by the patient's underlying immune state. Methods: A total of 111 sputum specimens and 64 bronchoalveolar lavage fluid (BALF) specimens were collected from 143 patients diagnosed with NTM-PD under different immune states. Metagenomic sequencing was performed on these specimens to characterize and compare the pulmonary microenvironmental features among NTM-PD patients with a distinct immune status through comprehensive bioinformatic analyses. Results: The immunosuppressed group exhibited a lower α-diversity in sputum specimens (p < 0.05). Principal Coordinates Analysis (PCoA) of β-diversity for sputum and BALF specimens revealed significant differences between the groups (p < 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis identified species enriched in the immunosuppressed group. A co-occurrence network analysis indicated that the immunosuppressed group had more structured and actively connected networks compared to the control group. The Mantel test confirmed that the abundance of these species enriched was associated with clinical immune-inflammation-related indicators in patients. Conclusions: Our study reveals the pulmonary microenvironment in immunosuppressed patients with NTM-PD. Further work is required to explore the two-way relationship between micro-organisms and immune and inflammatory responses, with the influence on patient outcomes.
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Affiliation(s)
- Le Qin
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Yu Chen
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
- Shanghai Institute of Infectious Disease and Biosecurity, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Sichun Luan
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Xiaoyu Yin
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Jue Pan
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Leilei Wang
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Yumeng Yao
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Chunmei Zhou
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (C.Z.); (R.B.); (J.S.)
| | - Rong Bao
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (C.Z.); (R.B.); (J.S.)
| | - Jiajin Shen
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (C.Z.); (R.B.); (J.S.)
| | - Qing Miao
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China; (L.Q.); (Y.C.); (S.L.); (X.Y.); (J.P.); (L.W.); (Y.Y.)
- Shanghai Institute of Infectious Disease and Biosecurity, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Isozaki Y, Makikawa T, Kimura K, Nishihara D, Fujino M, Tanaka Y, Hayashi C, Ishizaki Y, Igarashi M, Yokoyama T, Toshima K, Takahashi D. Creation of a macrolide antibiotic against non-tuberculous Mycobacterium using late-stage boron-mediated aglycon delivery. SCIENCE ADVANCES 2025; 11:eadt2352. [PMID: 40043128 PMCID: PMC11881915 DOI: 10.1126/sciadv.adt2352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/30/2025] [Indexed: 05/13/2025]
Abstract
Non-tuberculous mycobacteria (NTM) is gaining clinical recognition as a recently emerging pulmonary pathogen. Mycobacterium avium complex (MAC), the most common NTM, is the cause of pulmonary MAC disease. Currently, the macrolide azithromycin (AZM) is the standard first-line antibiotic for treatment of the disease. However, the rise of drug-resistant MAC necessitates the development of alternative therapeutics. Here, we present a late-stage boron-mediated aglycon delivery strategy for selective modification of AZM, generating a library of potential anti-MAC drugs designated KU01 to KU13. Screening of KU01 to KU13 revealed that KU13 exhibited enhanced antimicrobial activity against wild-type and macrolide-resistant MAC compared to AZM. Cryo-electron microscopy analysis indicated that the inserted tercyclic moiety of KU13 formed a robust anchor on the bacterial ribosome, creating a binding pocket with base flipping of U2847, potentially bypassing the standard mechanism of macrolide resistance. These results position KU13 as a promising lead for therapeutics against macrolide-resistant MAC.
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Affiliation(s)
- Yuka Isozaki
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
| | - Takumi Makikawa
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
| | - Kosuke Kimura
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
| | - Daiki Nishihara
- Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
| | - Maho Fujino
- Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
| | - Yoshikazu Tanaka
- Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
- The Advanced Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan
| | - Chigusa Hayashi
- Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
| | - Yoshimasa Ishizaki
- Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
| | - Masayuki Igarashi
- Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
| | - Takeshi Yokoyama
- Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan
- The Advanced Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan
| | - Kazunobu Toshima
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
| | - Daisuke Takahashi
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
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Li NN, Gao LL, Liu M, Zhang WM, Zhang XK, Chen L, Zong Z, Lan Y. Analysis of non-tuberculous mycobacteria types in high tuberculosis endemic areas. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:54. [PMID: 40022224 PMCID: PMC11871818 DOI: 10.1186/s41043-025-00765-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/21/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND The incidence of non-tuberculous mycobacteria (NTM) has been rising globally, posing significant challenges for diagnosis and treatment, particularly in regions with high tuberculosis (TB) incidence. This study aims to investigate the epidemiological, demographic, and clinical characteristics of non-tuberculous mycobacterial lung disease (NTM-PD) in areas with a high incidence of TB. METHOD This study was conducted at the Affiliated Hospital of Zunyi Medical University from January 2017 to December 2021. A total of 6259 culture-positive specimens were analyzed. Screening was based on acid-fast staining, colony morphology, and p-nitrobenzoic acid detection, which identified 107 suspected NTM strains. Gene sequencing confirmed 51 NTM-positive cases. RESULTS The predominant species identified were Mycobacterium abscessus (33.33%) and Mycobacterium intracellulare (27.45%). Several risk factors were associated with higher susceptibility to NTM-PD suspect, including bronchiectasis, low serum albumin levels (< 3.5 g/L), and male gender. The study found that although the isolation rate of NTM remained stable over the five-year period, drug resistance rates for the dominant species were notably high. CONCLUSIONS The findings highlight the need for clinicians in TB-endemic areas to carefully distinguish NTM infections from TB. The stable isolation rates of NTM, coupled with the high drug resistance of key species, underscore the importance of accurate diagnosis and tailored treatment strategies to manage NTM-PD effectively.
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Affiliation(s)
- Na-Na Li
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China.
- Innovation Center for Tuberculosis Comprehensive Prevention and Cure in Guizhou Province, Zunyi, 563003, China.
- The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, 563000, China.
| | - Lu-Lu Gao
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China
| | - Mei Liu
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China
| | - Wan-Min Zhang
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China
| | - Xiao-Ke Zhang
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China
| | - Ling Chen
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China.
- Innovation Center for Tuberculosis Comprehensive Prevention and Cure in Guizhou Province, Zunyi, 563003, China.
| | - Zhaojing Zong
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China
| | - Yuanbo Lan
- Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China.
- Innovation Center for Tuberculosis Comprehensive Prevention and Cure in Guizhou Province, Zunyi, 563003, China.
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Wazahat R. Strategic diagnosis- Unraveling Tuberculosis- A comprehensive approach. Indian J Tuberc 2025; 72:112-132. [PMID: 39890361 DOI: 10.1016/j.ijtb.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/22/2024] [Accepted: 08/12/2024] [Indexed: 02/03/2025]
Abstract
Tuberculosis, an airborne-infectious disease caused by Mycobacterium tuberculosis remains a perpetual threat globally. It claims over 1.4 million lives per year. Various diagnostic strategies including smear microscopy, culture methods, immunochromatographic assays and molecular methods have paved the way for tuberculosis diagnosis. The Government of India has introduced National Strategic Plan (NSP) for TB elimination, aiming to achieve a rapid decline in the incidence, morbidity, and mortality of TB by the year 2030. In its quest for TB elimination, the plan is structured around four strategic pillars: "Detect-Treat-Prevent-Build." To achieve these pillars and progress towards TB elimination, the government encourages adoption of novel point-of- care diagnostics techniques.
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Affiliation(s)
- Rushna Wazahat
- Department of Biochemistry, Jamia Hamdard, New Delhi, 110062, India.
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Imperiale BR, Mancino MB, Moyano RD, de la Barrera S, Morcillo NS. In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria. J Antibiot (Tokyo) 2024; 77:306-314. [PMID: 38438500 DOI: 10.1038/s41429-024-00709-3] [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: 09/21/2023] [Revised: 01/23/2024] [Accepted: 01/27/2024] [Indexed: 03/06/2024]
Abstract
Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult and with variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and to explore the cross-resistance with the currently used FQs.A total of 12 pre-extensively drug-resistant (XDR) Mtb, 2 XDR, 36 fully drug susceptible strains and 41 NTM isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimal inhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonary epithelial cells were also determined.DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, no cross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that were already resistant to LX/MOX.DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.
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Affiliation(s)
- Belén R Imperiale
- Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina.
| | - María B Mancino
- Dr. Cetrángolo Hospital, Florida, Buenos Aires Province, Argentina
| | - Roberto D Moyano
- IABIMO-CONICET, INTA CiCVyA, Hurlingham, Buenos Aires Province, Argentina
| | - Silvia de la Barrera
- Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina
| | - Nora S Morcillo
- Dr. Cetrángolo Hospital, Florida, Buenos Aires Province, Argentina
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Huang HY, Bu KP, Liu JW, Wei J. Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient: A case report. World J Clin Cases 2024; 12:2079-2085. [PMID: 38680269 PMCID: PMC11045514 DOI: 10.12998/wjcc.v12.i12.2079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 02/26/2024] [Accepted: 04/02/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Infections by non-tuberculous mycobacteria (NTM) have become more common in recent years. Mycobacterium canariasense (M. canariasense) was first reported as an opportunistic pathogen in 2004, but there have been very few case reports since then. Nocardia is a genus of aerobic and Gram-positive bacilli, and these species are also opportunistic pathogens and in the Mycobacteriales order. Conventional methods for diagnosis of NTM are inefficient. Metagenomic next-generation sequencing (mNGS) can rapidly detect many pathogenic microorganisms, even rare species. Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms. There are no previous reports of infection by M. canariasense and Nocardia farcinica (N. farcinica), especially in immunocompetent patients. This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M. canariasense, N. farcinica, and Candida parapsilosis (C. parapsilosis) based on mNGS. CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk, and recurrent episodes of moderate-grade fever for 1 wk. She received antibiotics for 1 wk at a local hospital, and experienced defervescence, but the productive cough and chest pain persisted. We collected samples of a lung lesion and alveolar lavage fluid for mNGS. The lung tissue was positive for M. canariasense, N. farcinica, and C. parapsilosis, and the alveolar lavage fluid was positive for M. canariasense. The diagnosis was pneumonia, and application of appropriate antibiotic therapy cured the patient. CONCLUSION Etiological diagnosis is critical for patients with infectious diseases. mNGS can identify rare and novel pathogens, and does not require a priori knowledge.
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Affiliation(s)
- Hai-Yan Huang
- Department of Comprehensive Internal Medicine, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Kun-Peng Bu
- Department of Comprehensive Internal Medicine, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jin-Wei Liu
- Department of Doppler Ultrasound, The Second Nanning People's Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jing Wei
- Department of Comprehensive Internal Medicine, The Affiliated Cancer Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Rola A, Gumienna-Kontecka E, Potocki S. Exploring binding preferences: Cu(II), Ni(II), and Zn(II) complexes of mycobacterial GroEL1 His-rich and Glu/His-rich domains. Dalton Trans 2024; 53:4054-4066. [PMID: 38305693 DOI: 10.1039/d3dt03579d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Mycobacterial histidine-rich GroEL1 protein significantly differs from the well-known methionine-glycine-rich GroEL chaperonin and most preferably participates in Cu(II) homeostasis. Some GroEL1 proteins, however, do not possess six but only three histidine residues and more acidic residues that can function as binding sites for metal ions. To evaluate the importance of this difference, we examined and compared the properties of GroEL1 His-rich or Glu/His-rich C-terminal domains as ligands for Cu(II), Ni(II), and Zn(II) ions. We studied the stoichiometry, stability, and binding sites of Cu(II)/Ni(II)/Zn(II) complexes of two model peptides: XEN = Ac-DKPEEEEDGHGHAH (M. xenopi) and ABS = Ac-DKPAEEADHGHGHHGHAH (M. abscessus) in the pH range 2-11. In the case of Cu(II), Ni(II), and Zn(II) complexes of XEN and ABS, ABS always formed more stable complexes. For XEN, there seemed to be no preference for Ni(II) or Zn(II) ions. In contrast, for ABS, Zn(II) formed a complex that was slightly more stable than the one formed by Ni(II). This may be due to the 6 His residues, which preferentially interact with Zn(II) rather than Ni(II). The study identified that an equilibrium of complexes-known as polymorphism-may occur in ABS complexes. Therefore, distinct sets of histidine residues may be involved in metal binding.
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Affiliation(s)
- Anna Rola
- Faculty of Chemistry, University of Wroclaw, 50-383 Wroclaw, Poland.
| | | | - Sławomir Potocki
- Faculty of Chemistry, University of Wroclaw, 50-383 Wroclaw, Poland.
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Maya T, Komba E, Mensah G, Mnyambwa N, Doulla B, Mfinanga S, Addo K, Kazwala R. Non-tuberculous mycobacterial pulmonary disease: Awareness survey of front-desk healthcare workers in Northern Tanzania. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0000741. [PMID: 36963008 PMCID: PMC10021751 DOI: 10.1371/journal.pgph.0000741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 12/01/2022] [Indexed: 01/22/2023]
Abstract
Over the past decade, there have been increasing reports of non-tuberculous mycobacteria (NTM) species being implicated in tuberculosis (TB) treatment failure or misdiagnosed as TB. Inadequate awareness of NTM pulmonary disease among healthcare workers (HCWs) may contribute to a low index of suspicion for patients presenting to their hospitals. In this study, we assessed the awareness of NTM pulmonary disease (NTM-PD) among front desk HCWs in Northern Tanzania. A cross-sectional descriptive survey was carried out among front desk HCWs in four administrative regions of Northern Tanzania. A standardized questionnaire was administered to consented participants from four clusters; clinicians, laboratory scientists, nurses, and pharmacists serving TB patients from Regional and District Health Facilities. Each participant was asked a set of questions, scored and the total score for each participant was determined. An awareness score was used to measure the level of awareness. The average score for all participants was estimated including the 95% confidence interval (CI). The overall awareness score was 24.1%, 95% CI 22.0-26.2%. History of training, experience in TB care, level of health facilities, age group, and setting were found to be statistically associated with the level of awareness of study participants. More than two-thirds (67%) of participants believe that pulmonary NTM and TB are clinically similar and 60% are not aware that AFB Microscopy cannot distinguish between the two. Only 13% of participants could mention at least one risk factor for NTM pulmonary disease. The level of awareness of NTM pulmonary disease was poor among HCWs in the surveyed TB clinics. National TB Programs are advised to include a topic on NTM in various on-job TB training packages for HCWs.
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Affiliation(s)
- Togolani Maya
- Department of Veterinary Medicine and Public Health, College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro, Tanzania
- Central Tuberculosis Reference Laboratory, National Tuberculosis and Leprosy Program, Dar es Salaam, Tanzania
| | - Erick Komba
- Department of Veterinary Medicine and Public Health, College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro, Tanzania
| | - Gloria Mensah
- Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Nicholaus Mnyambwa
- National Institute for Medical Research, Muhimbili Research Centre, Dar es Salaam, Tanzania
| | - Basra Doulla
- Central Tuberculosis Reference Laboratory, National Tuberculosis and Leprosy Program, Dar es Salaam, Tanzania
| | - Sayoki Mfinanga
- National Institute for Medical Research, Muhimbili Research Centre, Dar es Salaam, Tanzania
| | - Kennedy Addo
- Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
| | - Rudovick Kazwala
- Department of Veterinary Medicine and Public Health, College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro, Tanzania
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Quantitative evaluation of Mycobacterium abscessus clinical isolate virulence using a silkworm infection model. PLoS One 2022; 17:e0278773. [PMID: 36538550 PMCID: PMC9767372 DOI: 10.1371/journal.pone.0278773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/23/2022] [Indexed: 12/24/2022] Open
Abstract
Mycobacterium abscessus causes chronic skin infections, lung diseases, and systemic or disseminated infections. Here we investigated whether the virulence of M. abscessus clinical isolates could be evaluated by calculating the median lethal dose (LD50) in a silkworm infection model. M. abscessus subsp. abscessus cells were injected into the silkworm hemolymph. When reared at 37˚C, the silkworms died within 2 days post-infection with M. abscessus subsp. abscessus. Viable cell numbers of M. abscessus increased in the hemolymph of silkworms injected with M. abscessus. Silkworms were not killed by injections with heat-killed M. abscessus cells. The administration of clarithromycin, an antibacterial drug used to treat the infection in humans, prolonged the survival time of silkworms injected with M. abscessus. The LD50 values of 7 clinical isolates in the silkworm infection model were differed by up to 9-fold. The Mb-17 isolate, which was identified as a virulent strain in the silkworm infection model, induced more detachment of human THP-1-derived macrophages during infection than the Mb-10 isolate. These findings suggest that the silkworm M. abscessus infection model can be used to quantitatively evaluate the virulence of M. abscessus clinical isolates in a short time period.
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Aghajani J, Farnia P, Farnia P, Ghanavi J, Saif S, Marjani M, Tabarsi P, Moniri A, Abtahian Z, Hoffner S, Velayati AA. Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran. Int J Mycobacteriol 2022; 11:415-422. [PMID: 36510928 DOI: 10.4103/ijmy.ijmy_167_22] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.
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Affiliation(s)
- Jafar Aghajani
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Poopak Farnia
- Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parissa Farnia
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jalaledin Ghanavi
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shima Saif
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Marjani
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afshin Moniri
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Abtahian
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sven Hoffner
- Department of Global Public Health, Karolinska Institute, Stockholm, Sweden
| | - Ali Akbar Velayati
- Mycobacteriology Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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12
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Chen S, Wang F, Xue Y, Huo F, Jia J, Dong L, Zhao L, Jiang G, Huang H. Doubled Nontuberculous Mycobacteria Isolation as a Consequence of Changes in the Diagnosis Algorithm. Infect Drug Resist 2022; 15:3347-3355. [PMID: 35782527 PMCID: PMC9249383 DOI: 10.2147/idr.s368671] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 06/16/2022] [Indexed: 11/23/2022] Open
Abstract
Background Nontuberculous mycobacteria (NTM) and their associated diseases remain neglected. Through minor modifications in our diagnostic algorithm, we observed an unexpected higher number of cultivable NTM isolates. Therefore, a retrospective study was performed thoroughly to investigate the effect of changed laboratory procedures on NTM isolation in a specialized tuberculosis hospital. Methods NTM isolation rates and composition of NTM species were compared for the two diagnostic algorithms: (1) by using traditional p-nitrobenzoic acid (PNB) selective medium as a preliminary test to identify NTM isolates among the positive cultures (procedure I) and (2) by using the MPT64 antigen detection method to distinguish between Mycobacterium tuberculosis complex (MTBC) isolates and possible NTM isolates after a positive MGIT960 liquid culture (procedure II). Results The NTM isolation rate in procedure II was significantly higher than the procedure I (18.08% vs 9.71%; P<0.001). A noticeable increase in the ratio of NTM isolates among the identified mycobacteria was observed over the studied years (ie, from 58.18% in 2019 to 72.93% in 2021), which indicated a more precise prescription of species identification test after prompt information was provided in procedure II. In addition, the consistency of the identified species using multiple specimens from the same patient did not present a significant difference between the procedures. Conclusion According to our study, NTM infection might be far more underestimated than it is. A diagnostic procedure combining MGIT960 culture and MPT64 antigen detection could timely and easily identify clues of NTM isolates and improve the diagnosis of NTM infections.
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Affiliation(s)
- Suting Chen
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Fen Wang
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Yi Xue
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Fengmin Huo
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Junnan Jia
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Lingling Dong
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Liping Zhao
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Guanglu Jiang
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
| | - Hairong Huang
- National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China
- Correspondence: Hairong Huang, Email ; Guanglu Jiang,
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Yin H, Gu X, Wang Y, Fan G, Lu B, Liu M, Wang C, Cao B, Wang C. Clinical characteristics of patients with bronchiectasis with nontuberculous mycobacterial disease in Mainland China: a single center cross-sectional study. BMC Infect Dis 2021; 21:1216. [PMID: 34872515 PMCID: PMC8650543 DOI: 10.1186/s12879-021-06917-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/26/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The diagnosis and treatment of patients with bronchiectasis and nontuberculous mycobacterium (NTM) pulmonary disease are challenging issues and the treatment is also prolonged and depends on the species. There is limited information on patients with bronchiectasis and NTM pulmonary disease in Mainland China. METHODS This cross-sectional study was conducted at the China-Japan Friendship Hospital, Beijing, China. Those adult patients who met the diagnostic criteria for bronchiectasis and obtained a culture result of mycobacteria from lower respiratory tract specimens or lung tissue were included in this study. A logistic regression model was used to identify the related factors in patients with NTM pulmonary disease. RESULTS A total of 202 patients with bronchiectasis from 19 cities, 155 without and 47 (23.3%) with NTM pulmonary disease, were included. In all the 47 patients with NTM pulmonary disease, Mycobacterium avium complex was the most common species (66.0%), and 72.3% of them were initiated on standard anti-NTM treatment within 3 months after the diagnosis of NTM pulmonary disease. A larger proportion of patients with NTM pulmonary disease had acute exacerbations of ≥ 3 times within 1 year and were diagnosed bronchiectasis ≥ 50 years among patients with NTM pulmonary disease. The HRCT chest images revealed higher proportions of nodular shadow (100% vs. 35.3%), tree-in-bud sign (97.9% vs. 29.0%), cavities (29.8% vs. 5.8%), and airway dilation of the right middle lobe or the left lingular lobe (63.8% vs. 23.9%) in patients with NTM pulmonary disease than in those without NTM pulmonary disease (all P values = 0.001). The multivariable logistic regression model indicated that three and more abnormal features (OR 33.8; 95% CI 11.1-102.8) and main lesions of bronchial expansion in the middle or lingual lobe (OR 6.4; 95% CI 2.4-16.6) in HRCT chest images were independently associated with NTM pulmonary disease (P values = 0.001). CONCLUSION In a single center of Mainland China, > 23% of patients with bronchiectasis had NTM pulmonary disease, and most patients were started on standard treatment within 3 months after the diagnosis of NTM pulmonary disease. These findings suggest that patients with bronchiectasis should be thoroughly examined for the presence of NTM pulmonary disease. TRIAL REGISTRATION NCT03594032.
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Affiliation(s)
- Hongjun Yin
- Xuanwu Hospital of Capital Medical University, Beijing, China
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China
- Department of Infectious Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Xiaoying Gu
- Department of Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
- Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China
- National Clinical Research Center of Respiratory Diseases, Beijing, China
| | - Yimin Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China
- National Clinical Research Center of Respiratory Diseases, Beijing, China
| | - Guohui Fan
- Department of Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
- Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China
- National Clinical Research Center of Respiratory Diseases, Beijing, China
| | - Binghuai Lu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China
- Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan, Friendship Hospital, Beijing, China
| | - Min Liu
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
| | - Chunlei Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China
- Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan, Friendship Hospital, Beijing, China
| | - Bin Cao
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China.
- Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.
- Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China.
- Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.
| | - Chen Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, East Yinghua Road, Chaoyang District, Beijing, China.
- Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China.
- Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Bai A, Belda O, Dosanjh A. Pulmonary Nontuberculous Mycobacterial Infection in Infants: A Systematic Review. Pediatric Health Med Ther 2021; 12:551-559. [PMID: 35002357 PMCID: PMC8721029 DOI: 10.2147/phmt.s332434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/26/2021] [Indexed: 01/15/2023] Open
Abstract
Limited information and literature exist examining pulmonary infections caused by nontuberculous mycobacterial specifically in an infant population. The objective of our study was to summarize clinical characteristics and outcomes of infant patients with nontuberculous mycobacterial pulmonary infection via systematic literature review to identify common diagnostic and treatment regimens for this infection in infants. A search of MEDLINE and PubMed databases in October 2019 using MeSH search terms “infant,” “NTM,” “pulmonary,” and “Mycobacterium abscessus” yielded 139 articles. Inclusion criteria were i) English-language studies including cases and case series with ii) established nontuberculous mycobacterial pulmonary infection in iii) a patient population of infants no older than 24 months. Patients with cystic fibrosis and any study which did not contain relevant information such as infection and age were excluded. This yielded data on 37 patients extracted from 28 studies analyzed. The most common strain was Mycobacterium avium complex, isolated in 56.8% of patient diagnoses. Bronchoscopy/thoracoscopy with a subsequent culture were the most common diagnostic techniques, utilized in 64.9% of cases. Drug therapeutic treatment was utilized in 86% of cases, with a median of three drugs administered. Notable limitations of this study are the small sample size and its retrospective nature, which relies on information reported in previous case studies. Although there is limited formal clinician consensus on the treatment of NTM pulmonary infection and how it may differ in an infant population, our findings indicate an informal consensus typically involving diagnostic lung specimen culture and antibiotic therapy.
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Affiliation(s)
- Alice Bai
- Brown University, Providence, RI, USA
- Correspondence: Alice Bai Brown University, 69 Brown St. Mail# 5288, Providence, RI, 02912, USATel +1 770 843-2062 Email
| | | | - Amrita Dosanjh
- Pediatric Respiratory, Affiliated Staff Member, Department of Pediatrics, Rady Children’s Hospital, San Diego, CA, USA
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15
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Adekanmbi O, Lakoh S. A case report of pneumonia due to non-tuberculous mycobacteria in an immunocompetent patient. Pan Afr Med J 2021; 38:412. [PMID: 34381556 PMCID: PMC8325462 DOI: 10.11604/pamj.2021.38.412.21501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/17/2021] [Indexed: 11/11/2022] Open
Abstract
Non-tuberculous mycobacteria are uncommon pathogens in immunocompetent individuals. We report an unusual case of pneumonia with pleural effusion caused by co-infection with two species of non-tuberculous mycobacteria in an immunocompetent man in Nigeria. The case highlights the possibility of the occurrence of a disease caused by these pathogens in an unusual host in a setting where they are rarely isolated as well as the challenges faced in diagnosis.
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Affiliation(s)
- Olukemi Adekanmbi
- College of Medicine, University of Ibadan, Ibadan, Nigeria.,University College Hospital, Ibadan, Nigeria
| | - Sulaiman Lakoh
- College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.,University of Sierra Leone Teaching Hospitals Complex, Freetown, Sierra Leone
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16
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Victoria L, Gupta A, Gómez JL, Robledo J. Mycobacterium abscessus complex: A Review of Recent Developments in an Emerging Pathogen. Front Cell Infect Microbiol 2021; 11:659997. [PMID: 33981630 PMCID: PMC8108695 DOI: 10.3389/fcimb.2021.659997] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/07/2021] [Indexed: 01/04/2023] Open
Abstract
Mycobacterium abscessus complex (MABC) is one of the most clinically relevant species among nontuberculous mycobacteria. MABC's prevalence has increased over the last two decades. Although these changes can be explained by improvements in microbiological and molecular techniques for identifying species and subspecies, a higher prevalence of chronic lung diseases may contribute to higher rates of MABC. High rates of antimicrobial resistance are seen in MABC, and patients experience multiple relapses with low cure rates. This review aims to integrate existing knowledge about MABC epidemiology, microbiological identification and familiarize readers with molecular mechanisms of resistance and therapeutic options for pulmonary infections with MABC.
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Affiliation(s)
- Laura Victoria
- Laboratory of Bacteriology and Mycobacteria, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.,Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Amolika Gupta
- Pulmonary, Critical Care and Sleep Medicine Section, Yale University School of Medicine, New Haven, CT, United States
| | - Jose Luis Gómez
- Pulmonary, Critical Care and Sleep Medicine Section, Yale University School of Medicine, New Haven, CT, United States
| | - Jaime Robledo
- Laboratory of Bacteriology and Mycobacteria, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.,Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia
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17
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Lotfi H, Aryan E, Sankian M, Meshkat Z, Khalifeh Soltani A, Alvandi AH, Farsiani H. A case of multidrug-resistant Mycobacterium simiae in an elderly woman. Respirol Case Rep 2021; 9:e00715. [PMID: 33552522 PMCID: PMC7848708 DOI: 10.1002/rcr2.715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/27/2020] [Accepted: 01/11/2021] [Indexed: 11/22/2022] Open
Abstract
Mycobacterium simiae is an emerging and spreading pathogen in Iran and little data about its drug susceptibility test (DST) and no standard treatment regimen are available. We report a case of multidrug-resistant M. simiae respiratory infection in a 65-year-old woman with a history of previous Mycobacterium tuberculosis infection. The patient was treated with clarithromycin, levofloxacin, and cotrimoxazole for one year and eventually died while still suffering from respiratory problems. For DST, broth microdilution method was used according to the Clinical and Laboratory Standards Institute guidelines as well as molecular DST in clinical isolate. Mycobacterium simiae was resistant to streptomycin, moxifloxacin, clarithromycin, and cotrimoxazole antibiotics and was sensitive to clofazimine and amikacin antibiotics. Inappropriate use of antibiotics without determining the pattern of antibiotic resistance increases the likelihood of resistance and, for resistant specimens, the need to review the treatment protocol and replace antibiotics. Effectiveness based on antibiotic resistance pattern is essential.
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Affiliation(s)
- Hadi Lotfi
- Antimicrobial Resistance Research CenterMashhad University of Medical SciencesMashhadIran
- Laboratory of Microbiology, Department of Medical MicrobiologyGhaem University Hospital, Mashhad University of Medical SciencesMashhadIran
| | - Ehsan Aryan
- Antimicrobial Resistance Research CenterMashhad University of Medical SciencesMashhadIran
- Laboratory of Microbiology, Department of Medical MicrobiologyGhaem University Hospital, Mashhad University of Medical SciencesMashhadIran
| | - Mojtaba Sankian
- Immunobiochemistry Laboratory, Immunology Research CenterMashhad University of Medical SciencesMashhadIran
| | - Zahra Meshkat
- Antimicrobial Resistance Research CenterMashhad University of Medical SciencesMashhadIran
- Laboratory of Microbiology, Department of Medical MicrobiologyGhaem University Hospital, Mashhad University of Medical SciencesMashhadIran
| | - Ahmad Khalifeh Soltani
- Department of Infectious Diseases and Tropical Medicine, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Amir Hooshang Alvandi
- Department of Medical MicrobiologyKermanshah University of Medical SciencesKermanshahIran
| | - Hadi Farsiani
- Antimicrobial Resistance Research CenterMashhad University of Medical SciencesMashhadIran
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Lopez A, Shoen C, Cynamon M, Dimitrakopoulou D, Paiola M, Pavelka MS, Robert J. Developing Tadpole Xenopus laevis as a Comparative Animal Model to Study Mycobacterium abscessus Pathogenicity. Int J Mol Sci 2021; 22:E806. [PMID: 33467397 PMCID: PMC7829954 DOI: 10.3390/ijms22020806] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/11/2021] [Accepted: 01/12/2021] [Indexed: 12/19/2022] Open
Abstract
Mycobacterium abscessus (Mab) is an emerging, nontuberculosis mycobacterium (NTM) that infects humans. Mab has two morphotypes, smooth (S) and rough (R), related to the production of glycopeptidolipid (GPL), that differ in pathogenesis. To further understand the pathogenicity of these morphotypes in vivo, the amphibian Xenopus laevis was used as an alternative animal model. Mab infections have been previously modeled in zebrafish embryos and mice, but Mab are cleared early from immunocompetent mice, preventing the study of chronic infection, and the zebrafish model cannot be used to model a pulmonary infection and T cell involvement. Here, we show that X. laevis tadpoles, which have lungs and T cells, can be used as a complementary model for persistent Mab infection and pathogenesis. Intraperitoneal (IP) inoculation of S and R Mab morphotypes disseminated to tadpole tissues including liver and lungs, persisting for up to 40 days without significant mortality. Furthermore, the R morphotype was more persistent, maintaining a higher bacterial load at 40 days postinoculation. In contrast, the intracardiac (IC) inoculation with S Mab induced significantly greater mortality than inoculation with the R Mab form. These data suggest that X. laevis tadpoles can serve as a useful comparative experimental organism to investigate pathogenesis and host resistance to M. abscessus.
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Affiliation(s)
- Arianna Lopez
- Department of Immunology and Microbiology, Medical Center, University of Rochester, Rochester, NY 14642, USA; (A.L.); (D.D.); (M.P.); (M.S.P.J.)
| | - Carolyn Shoen
- Central New York Research Corporation, Syracuse, NY 13210, USA; (C.S.); (M.C.)
| | - Michael Cynamon
- Central New York Research Corporation, Syracuse, NY 13210, USA; (C.S.); (M.C.)
- Veterans Affairs Medical Center, Syracuse, NY 13210, USA
| | - Dionysia Dimitrakopoulou
- Department of Immunology and Microbiology, Medical Center, University of Rochester, Rochester, NY 14642, USA; (A.L.); (D.D.); (M.P.); (M.S.P.J.)
| | - Matthieu Paiola
- Department of Immunology and Microbiology, Medical Center, University of Rochester, Rochester, NY 14642, USA; (A.L.); (D.D.); (M.P.); (M.S.P.J.)
| | - Martin S. Pavelka
- Department of Immunology and Microbiology, Medical Center, University of Rochester, Rochester, NY 14642, USA; (A.L.); (D.D.); (M.P.); (M.S.P.J.)
| | - Jacques Robert
- Department of Immunology and Microbiology, Medical Center, University of Rochester, Rochester, NY 14642, USA; (A.L.); (D.D.); (M.P.); (M.S.P.J.)
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Byrne AS, Goudreau A, Bissonnette N, Shamputa IC, Tahlan K. Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review. Front Genet 2020; 11:600692. [PMID: 33408740 PMCID: PMC7779811 DOI: 10.3389/fgene.2020.600692] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 11/19/2020] [Indexed: 12/22/2022] Open
Abstract
Mixed strain infection (MSI) refers to the concurrent infection of a susceptible host with multiple strains of a single pathogenic species. Known to occur in humans and animals, MSIs deserve special consideration when studying transmission dynamics, evolution, and treatment of mycobacterial diseases, notably tuberculosis in humans and paratuberculosis (or Johne's disease) in ruminants. Therefore, a systematic review was conducted to examine how MSIs are defined in the literature, how widespread the phenomenon is across the host species spectrum, and to document common methods used to detect such infections. Our search strategy identified 121 articles reporting MSIs in both humans and animals, the majority (78.5%) of which involved members of the Mycobacterium tuberculosis complex, while only a few (21.5%) examined non-tuberculous mycobacteria (NTM). In addition, MSIs exist across various host species, but most reports focused on humans due to the extensive amount of work done on tuberculosis. We reviewed the strain typing methods that allowed for MSI detection and found a few that were commonly employed but were associated with specific challenges. Our review notes the need for standardization, as some highly discriminatory methods are not adapted to distinguish between microevolution of one strain and concurrent infection with multiple strains. Further research is also warranted to examine the prevalence of NTM MSIs in both humans and animals. In addition, it is envisioned that the accurate identification and a better understanding of the distribution of MSIs in the future will lead to important information on the epidemiology and pathophysiology of mycobacterial diseases.
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Affiliation(s)
| | - Alex Goudreau
- Science & Health Sciences Librarian, University of New Brunswick, Saint John, NB, Canada
| | - Nathalie Bissonnette
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Isdore Chola Shamputa
- Department of Nursing & Health Sciences, University of New Brunswick, Saint John, NB, Canada
| | - Kapil Tahlan
- Department of Biology, Memorial University of Newfoundland, St. John's, NL, Canada
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Hernández-Jarguín AM, Martínez-Burnes J, Molina-Salinas GM, de la Cruz-Hernández NI, Palomares-Rangel JL, López Mayagoitia A, Barrios-García HB. Isolation and Histopathological Changes Associated with Non-Tuberculous Mycobacteria in Lymph Nodes Condemned at a Bovine Slaughterhouse. Vet Sci 2020; 7:vetsci7040172. [PMID: 33182568 PMCID: PMC7712099 DOI: 10.3390/vetsci7040172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/04/2020] [Accepted: 11/08/2020] [Indexed: 01/11/2023] Open
Abstract
Background: non-tuberculous mycobacteria (NTM) infect humans and animals and have a critical confounding effect on the diagnosis of bovine tuberculosis. The Official Mexican Standard (Norma Oficial Mexicana, NOM-ZOO-031-1995) for food safety regulates Mycobacterium bovis in cattle, but not the NTM species. The study's objective was to isolate and identify the NTM present in condemned bovine lymph nodes in a slaughterhouse, characterize the histological lesions, and correlate bacteriological and microscopic findings with the antemortem tuberculin skin test. Methods: from 528 cattle, one or two pooled samples of lymph nodes from each animal were cultured for Mycobacteria spp. and processed for histopathology. Results: mycobacteria were isolated from 54/528 (10.2%) of the condemned lymph nodes; 25/54 (46.2%) of these isolates were NTM; 4 bacteriological cultures with fungal contamination were discarded. Granulomatous and pyogranulomatous inflammation were present in 6/21 (28.6%) and 7/21 (33.3%) of the NTM-positive lymph nodes, respectively. The species of NTM associated with granulomatous lymphadenitis were M. scrofulaceum, M. triviale, M. terrae, and M. szulgai, while those causing pyogranulomatous lesions were M. szulgai, M. kansasii, M. phlei, and M. scrofulaceum. Conclusions: the NTM infections can cause false-positive results in the tuberculin test because of cross immune reactivity and interference with the postmortem identification of M. bovis in cattle.
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Affiliation(s)
- Angélica M. Hernández-Jarguín
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tamaulipas. Cd. Victoria, Tamaulipas C.P. 87000, Mexico; (J.M.-B.); (N.I.d.l.C.-H.); (J.L.P.-R.); (H.B.B.-G.)
- Correspondence:
| | - Julio Martínez-Burnes
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tamaulipas. Cd. Victoria, Tamaulipas C.P. 87000, Mexico; (J.M.-B.); (N.I.d.l.C.-H.); (J.L.P.-R.); (H.B.B.-G.)
| | - Gloria M. Molina-Salinas
- Unidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad Hospital de Especialidades 1 Mérida, Yucatán, Instituto Mexicano del Seguro Social, CP 97150, Mexico;
| | - Ned I. de la Cruz-Hernández
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tamaulipas. Cd. Victoria, Tamaulipas C.P. 87000, Mexico; (J.M.-B.); (N.I.d.l.C.-H.); (J.L.P.-R.); (H.B.B.-G.)
| | - José L. Palomares-Rangel
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tamaulipas. Cd. Victoria, Tamaulipas C.P. 87000, Mexico; (J.M.-B.); (N.I.d.l.C.-H.); (J.L.P.-R.); (H.B.B.-G.)
| | - Alfonso López Mayagoitia
- Department of Pathology & Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A4P3, Canada;
| | - Hugo B. Barrios-García
- Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tamaulipas. Cd. Victoria, Tamaulipas C.P. 87000, Mexico; (J.M.-B.); (N.I.d.l.C.-H.); (J.L.P.-R.); (H.B.B.-G.)
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Luukinen BV, Vuento R, Hirvonen JJ. Evaluation of a semi-automated Seegene PCR workflow with MTB, MDR, and NTM detection for rapid screening of tuberculosis in a low-prevalence setting. APMIS 2020; 128:406-413. [PMID: 32202675 DOI: 10.1111/apm.13040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 03/02/2020] [Indexed: 11/28/2022]
Abstract
In areas of low tuberculosis (TB) prevalence, laboratory diagnosis of TB may essentially cover non-tuberculous mycobacteria (NTM) in addition to Mycobacterium tuberculosis (MTB). In this study, a semi-automated PCR workflow distinguishing MTB and NTM (Anyplex™ MTB/NTMe, Seegene) and subsequently detecting MTB isoniazid/rifampicin resistance (Allplex™ MTB/MDRe, Seegene) was evaluated for replacing smear microscopy of acid-fast bacilli as the rapid screening method for TB. With 279 clinical samples, 47 cultures positive for MTB and 76 for NTM, the Anyplex™ MTB/NTMe assay and smear microscopy showed equal sensitivities (49.6% vs 50.8%, respectively) but Anyplex™ MTB/NTMe was more sensitive for MTB (63.8% vs 25.6%) than for NTM (40.8% vs 64.5%). Allplex™ MTB/MDRe showed a slightly higher sensitivity of 68.1% for MTB (32/47 positive, n = 222). Antibiotic resistance profiles were correctly identified for all MTB isolates (one MDR isolate). Specificity was 100% for both assays. Anyplex™ MTB/NTMe detected all the 18 NTM species present in the study. The analytical performance of the evaluated high-throughput workflow was relatively weak compared to culture but potentially adequate as a rapid screening method analogous to smear microscopy with additional differentiation between TB, MDR-TB, and NTM.
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Affiliation(s)
- Bruno Vincent Luukinen
- Department of Clinical Microbiology, Fimlab Laboratories, Tampere, Finland.,Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Risto Vuento
- Department of Clinical Microbiology, Fimlab Laboratories, Tampere, Finland
| | - Jari Juhani Hirvonen
- Department of Clinical Microbiology, Fimlab Laboratories, Tampere, Finland.,Mobidiag, Espoo, Finland
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22
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Kim BR, Kim BJ, Kook YH, Kim BJ. Mycobacterium abscessus infection leads to enhanced production of type 1 interferon and NLRP3 inflammasome activation in murine macrophages via mitochondrial oxidative stress. PLoS Pathog 2020; 16:e1008294. [PMID: 32210476 PMCID: PMC7094820 DOI: 10.1371/journal.ppat.1008294] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 12/23/2019] [Indexed: 01/01/2023] Open
Abstract
Mycobacterium abscessus (MAB) is a rapidly growing mycobacterium (RGM), and infections with this pathogen have been increasing worldwide. Recently, we reported that rough type (MAB-R) but not smooth type (MAB-S) strains enhanced type 1 interferon (IFN-I) secretion via bacterial phagosome escape, contributing to increased virulence. Here, we sought to investigate the role of mitochondrial oxidative stress in bacterial survival, IFN-I secretion and NLRP3 inflammasome activation in MAB-infected murine macrophages. We found that live but not heat-killed (HK) MAB-R strains increased mitochondrial ROS (mtROS) and increased release of oxidized mitochondrial DNA (mtDNA) into the cytosol of murine macrophages compared to the effects of live MAB-S strains, resulting in enhanced NLRP3 inflammasome-mediated IL-1β and cGAS-STING-dependent IFN-I production. Treatment of the infected macrophages with mtROS-modulating agents such as mito-TEMPO or cyclosporin A reduced cytosolic oxidized mtDNA, which inhibited the MAB-R strain-induced production of IL-1β and IFN-I. The reduced cytosolic oxidized mtDNA also inhibited intracellular growth of MAB-R strains via cytosolic escape following phagosomal rupture and via IFN-I-mediated cell-to-cell spreading. Moreover, our data showed that mtROS-dependent IFN-I production inhibited IL-1β production, further contributing to MAB-R intracellular survival in murine macrophages. In conclusion, our data indicated that MAB-R strains enhanced IFN-I and IL-1β production by inducing mtROS as a pathogen-associated molecular pattern (PAMP). These events also enhance bacterial survival in macrophages and dampen inflammation, which contribute to the pathogenesis of MAB-R strains.
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Affiliation(s)
- Bo-Ram Kim
- Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
| | - Byoung-Jun Kim
- Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
| | - Yoon-Hoh Kook
- Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
| | - Bum-Joon Kim
- Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea
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In Vitro Susceptibility Testing of GSK656 against Mycobacterium Species. Antimicrob Agents Chemother 2020; 64:AAC.01577-19. [PMID: 31791947 DOI: 10.1128/aac.01577-19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 11/25/2019] [Indexed: 02/03/2023] Open
Abstract
In this study, we aimed to assess the in vitro susceptibility to GSK656 among multiple mycobacterial species and to investigate the correlation between leucyl-tRNA synthetase (LeuRS) sequence variations and in vitro susceptibility to GSK656 among mycobacterial species. A total of 187 mycobacterial isolates, comprising 105 Mycobacterium tuberculosis isolates and 82 nontuberculous mycobacteria (NTM) isolates, were randomly selected for the determination of in vitro susceptibility. For M. tuberculosis, 102 of 105 isolates had MICs of ≤0.5 mg/liter, demonstrating a MIC50 of 0.063 mg/liter and a MIC90 of 0.25 mg/liter. An epidemiological cutoff value of 0.5 mg/liter was proposed for identification of GSK656-resistant M. tuberculosis strains. For NTM, the MIC50 and MIC90 values were >8.0 mg/liter for both Mycobacterium intracellulare and Mycobacterium avium In contrast, all Mycobacterium abscessus isolates had MICs of ≤0.25 mg/liter, yielding a MIC90 of 0.063 mg/liter. LeuRS from M. abscessus showed greater sequence similarity to M. tuberculosis LeuRS than to LeuRSs from M. avium and M. intracellulare Sequence alignment revealed 28 residues differing between LeuRSs from M. avium and M. intracellulare and LeuRSs from M. tuberculosis and M. abscessus; among them, 15 residues were in the drug binding domain. Structure modeling revealed that several different residues were close to the tRNA-LeuRS interface or the entrance of the drug-tRNA binding pocket. In conclusion, our data demonstrate significant species diversity in in vitro susceptibility to GSK656 among various mycobacterial species. GSK656 has potent efficacy against M. tuberculosis and M. abscessus, whereas inherent resistance was noted for M. intracellulare and M. avium.
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Comparison of chest X-ray lesion characteristics of multidrug-resistant tuberculosis and non-tuberculous mycobacterial infection. Pol J Radiol 2019; 84:e162-e170. [PMID: 31481986 PMCID: PMC6717943 DOI: 10.5114/pjr.2019.84515] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/04/2019] [Indexed: 11/17/2022] Open
Abstract
Purpose This research aimed to compared chest radiographic characteristics of multidrug-resistant tuberculosis (MDR-TB) and non-tuberculous mycobacteria (NTM) infection, which can be used in early diagnostic screening. Material and methods The method of this study was cross-sectional to obtain the relationship between radiographic findings. Results Among 538 subjects who were positive for TB during screening, 11 (2.04%) had MDR-TB, 147 (27.32%) had drug-sensitive TB, and 380 (70.63%) had NTM infection. The radiographic findings that correlated with MDR-TB were infiltrates (p = 0.010), cavities (p = 0.021), nodules (p = 0.001), and fibrosis (p = 0.010), with the best predictor of MDR-TB lesions being the presence of a nodule. The lesion locations related to MDR-TB were the upper right and left lung (p = 0.00). There were no specific lesions present in NTM infection (p < 0.05) because almost all had a meaningful correlation (p < 0.05), except the presence of a mass. The lesion location related to NTM infection was the medial aspect of the left lung (p = 0.01), and the lesion extent was also correlated (p < 0.05). Conclusions Chest X-ray lesion characteristics of MDR-TB show significant correlation among cavities, nodules, and fibrosis. There were no specific lesions that could differentiate NTM infection from MDR-TB; however, the most common lesion location in NTM infection was the medial aspect of the left lung.
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25
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LEDWOŃ ALEKSANDRA, NAPIÓRKOWSKA AGNIESZKA, AUGUSTYNOWICZ- KOPEĆ EWA, SZELESZCZUK PIOTR. Drug Susceptibility of Non-tuberculous Strains of Mycobacterium Isolated from Birds from Poland. Pol J Microbiol 2019; 67:487-492. [PMID: 30550235 PMCID: PMC7256868 DOI: 10.21307/pjm-2018-057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 09/16/2018] [Accepted: 09/17/2018] [Indexed: 11/24/2022] Open
Abstract
Mycobacterioses are a constant problem in backyard poultry, as well as pet birds. To date, no evidence of direct transmission of atypical bacilli between humans has been demonstrated, but it cannot be ruled out that sick animals can be a source of infection for people in their environment. The aim of the study was to identify mycobacteria isolated from birds with diagnosed mycobacteriosis and to determine the susceptibility of mycobacterial isolates from these animals to antituberculous drugs most commonly used in the treatment of mycobacterial infections in humans. For drug susceptibility tests, drugs such as isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, capreomycin, cycloserine and ethionamide were used. A high degree of drug resistance was demonstrated, particularly in Mycobacterium avium . Isolates of Mycobacterium xenopi showed a relatively good susceptibility to the drugs tested. The drug resistance of Mycobacterium genavense has not been determined, but this mycobacterium was identified in ten cases, which is the second most frequent occurrence in the cases studied. Mycobacterioses are a constant problem in backyard poultry, as well as pet birds. To date, no evidence of direct transmission of atypical bacilli between humans has been demonstrated, but it cannot be ruled out that sick animals can be a source of infection for people in their environment. The aim of the study was to identify mycobacteria isolated from birds with diagnosed mycobacteriosis and to determine the susceptibility of mycobacterial isolates from these animals to antituberculous drugs most commonly used in the treatment of mycobacterial infections in humans. For drug susceptibility tests, drugs such as isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, capreomycin, cycloserine and ethionamide were used. A high degree of drug resistance was demonstrated, particularly in Mycobacterium avium. Isolates of Mycobacterium xenopi showed a relatively good susceptibility to the drugs tested. The drug resistance of Mycobacterium genavense has not been determined, but this mycobacterium was identified in ten cases, which is the second most frequent occurrence in the cases studied.
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Affiliation(s)
- ALEKSANDRA LEDWOŃ
- Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences, Warsaw, Poland
| | - AGNIESZKA NAPIÓRKOWSKA
- Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - EWA AUGUSTYNOWICZ- KOPEĆ
- Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
| | - PIOTR SZELESZCZUK
- Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences, Warsaw, Poland
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Kim BR, Kim BJ, Kook YH, Kim BJ. Phagosome Escape of Rough Mycobacterium abscessus Strains in Murine Macrophage via Phagosomal Rupture Can Lead to Type I Interferon Production and Their Cell-To-Cell Spread. Front Immunol 2019; 10:125. [PMID: 30766538 PMCID: PMC6365470 DOI: 10.3389/fimmu.2019.00125] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 01/15/2019] [Indexed: 12/27/2022] Open
Abstract
Mycobacterium abscessus complex (MAB) is a rapidly growing mycobacterium(RGM) whose clinical significance as an emerging human pathogen has been increasing worldwide. It has two types of colony morphology, a smooth (S) type, producing high glycopeptidolipid (GPL) content, and a rough (R) type, which produces low levels of GPLs and is associated with increased virulence. However, the mechanism responsible for their difference in virulence is poorly known. By ultrastructural examination of murine macrophages infected, we found that MAB-R strains could replicate more actively in the macrophage phagosome than the S variants and that they could escape into cytosol via phagosomal rupture. The cytosolic access of MAB-R strains via phagosomal rupture led to enhanced Type I interferon (IFN) production and cell death, which resulted in their cell-to-cell spreading. This behavior can provide an additional niche for the survival of MAB-R strains. In addition, we found that their enhancement of cell death mediated cell spreading are dependent on Type I IFN signaling via comparison of wild-type and IFNAR1 knockout mice. In conclusion, our data indicated that a transition of MAB-S strains into MAB-R variants increased their virulence via enhanced Type I IFN production, which led to enhanced survival in infected macrophage via cell death mediated cell-to-cell spreading. This result provides not only a novel insight into the difference in virulence between MAB-R and -S variants but also hints to their treatment strategy.
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Affiliation(s)
| | | | | | - Bum-Joon Kim
- Department of Microbiology and Immunology, Biomedical Sciences, Liver Research Institute and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
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Aliberti S, Codecasa LR, Gori A, Sotgiu G, Spotti M, Di Biagio A, Calcagno A, Nardini S, Assael BM, Tortoli E, Besozzi G, Ferrarese M, Matteelli A, Girardi E, De Lorenzo S, Seia M, Gramegna A, Del Prato B, Terranova L, Oriano M, Sverzellati N, Mirsaeidi M, Chalmers JD, Haworth CS, Loebinger MR, Aksamit T, Winthrop K, Ringshausen FC, Previdi G, Blasi F. The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol. Multidiscip Respir Med 2018; 13:33. [PMID: 30151192 PMCID: PMC6101082 DOI: 10.1186/s40248-018-0141-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration Clinicaltrial.gov: NCT03339063.
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Affiliation(s)
- Stefano Aliberti
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Luigi Ruffo Codecasa
- Regional TB Reference Centre, Istituto Villa Marelli, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Gori
- 4Clinic of Infectious Diseases, 'San Gerardo" Hospital-ASST Monza, University Milano-Bicocca, Milan, Italy
| | - Giovanni Sotgiu
- 5Clinical Epidemiology and Medical Statistics Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Maura Spotti
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Antonio Di Biagio
- 6Clinica Malattie Infettive, Policlinico Ospedale S. Martino, Genoa, Italy
| | - Andrea Calcagno
- 7Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy
| | - Stefano Nardini
- 8Ospedale Civile, Pulmonary and TB Unit, Vittorio Veneto, Italy
| | - Baroukh Maurice Assael
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Enrico Tortoli
- 9Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Maurizio Ferrarese
- Regional TB Reference Centre, Istituto Villa Marelli, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Alberto Matteelli
- 11WHO Collaborating Centre for TB/HIV co-infection and TB Elimination, Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy
| | - Enrico Girardi
- Clinical Epidemiology Unit, National Institute for Infectious Disease "L. Spallanzani, Rome, Italy
| | - Saverio De Lorenzo
- E. Morelli Hospital ASST, Reference Center for MDR-TB and HIV-TB, Sondalo, Italy
| | - Manuela Seia
- 14Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Gramegna
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Bruno Del Prato
- 15Unit of Interventional Pulmonology, High Speciality "A. Cardarelli" Hospital, Naples, Italy
| | - Leonardo Terranova
- 16Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Martina Oriano
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Nicola Sverzellati
- 17Scienze Radiologiche, Dipartimento di Medicina e Chirurgia, Università di Parma, Parma, Italy
| | - Mehdi Mirsaeidi
- 18Miami Veterans Administration Medical Center, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Miami School of Medicine, Miami, FL USA
| | - James D Chalmers
- Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| | - Charles S Haworth
- 20Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK
| | | | | | - Kevin Winthrop
- 23Oregon Health and Science University, Portland, OR USA
| | - Felix C Ringshausen
- 24Dept of Respiratory Medicine, Member of the German Centre for Lung Research, Hannover Medical School, Hannover, Germany
| | - Giuliana Previdi
- Aziende Socio Sanitarie Territoriale Melegnano e della Martesana, Vizzolo Predabissi, Milan, Italy
| | - Francesco Blasi
- 1Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.,2Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
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Mycobacterioses identified in the National Reference Laboratory of Colombia from 2012 to 2016. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2018; 38:87-94. [PMID: 30184369 DOI: 10.7705/biomedica.v38i0.4143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 04/04/2018] [Indexed: 11/21/2022]
Abstract
Introduction: In recent years, there has been an increase in the prevalence of mycobacterioses caused by non-tuberculous mycobacteria, which are considered as emerging pathogens. Their presence depends on several factors such as the clinical history, the health status of the affected person, and the presence of these microorganisms in the water, the soil, and the animals, among others.
Objective: To describe the mycobacteria and the etiological agent identified in isolates received at the Laboratorio Nacional de Referencia de Micobacterias of the Instituto Nacional de Salud between 2012 and 2016.
Materials and methods: We conducted a retrospective analysis of samples from 273 patients with mycobacterioses. We analyzed the following variables: mycobacteriosis type, etiological agent, and associated predisposing factors.
Results: 57.1% of the cases presented pulmonary mycobacteriosis; 26%, cutaneous; 10.6%, disseminated, and 2.6%, lymphatic. We found the Mycobacterium avium complex more frequently in pulmonary mycobacteriosis, while M. abscessus was more frequent in the extrapulmonary types of the disease. Patients with pulmonary mycobacteriosis had a history of tuberculosis more frequently than those with extrapulmonary forms.
Conclusion: These findings highlight the importance of the differential diagnosis between M. tuberculosis complex species and non-tuberculous mycobacteria since the latter are genetically resistant to conventional antituberculosis drugs.
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Lai HC, Chang CJ, Lin CS, Wu TR, Hsu YJ, Wu TS, Lu JJ, Martel J, Ojcius DM, Ku CL, Young JD, Lu CC. NK Cell-Derived IFN-γ Protects against Nontuberculous Mycobacterial Lung Infection. THE JOURNAL OF IMMUNOLOGY 2018; 201:1478-1490. [PMID: 30061197 DOI: 10.4049/jimmunol.1800123] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 07/05/2018] [Indexed: 01/09/2023]
Abstract
In developed countries, pulmonary nontuberculous mycobacteria (NTM) infections are more prevalent than Mycobacterium tuberculosis infections. Given the differences in the pathogenesis of NTM and M. tuberculosis infections, separate studies are needed to investigate the pathological effects of NTM pathogens. Our previous study showed that anti-IFN-γ autoantibodies are detected in NTM-infected patients. However, the role of NK cells and especially NK cell-derived IFN-γ in this context has not been studied in detail. In the current study, we show that NK1.1 cell depletion increases bacterial load and mortality in a mouse model of pulmonary NTM infection. NK1.1 cell depletion exacerbates NTM-induced pathogenesis by reducing macrophage phagocytosis, dendritic cell development, cytokine production, and lung granuloma formation. Similar pathological phenomena are observed in IFN-γ-deficient (IFN-γ-/-) mice following NTM infection, and adoptive transfer of wild-type NK cells into IFN-γ-/- mice considerably reduces NTM pathogenesis. Injection of rIFN-γ also prevents NTM-induced pathogenesis in IFN-γ-/- mice. We observed that NK cells represent the main producers of IFN-γ in the lungs and production starts as soon as 1 d postinfection. Accordingly, injection of rIFN-γ into IFN-γ-/- mice 1 d (but not 2 wk) postinfection significantly improves immunity against NTM infection. NK cells also stimulate mycobacterial killing and IL-12 production by macrophages. Our results therefore indicate that IFN-γ production by NK cells plays an important role in activating and enhancing innate and adaptive immune responses at early stages of pulmonary NTM infection.
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Affiliation(s)
- Hsin-Chih Lai
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Microbiota Research Center, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Research Center for Emerging Viral Infections, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taoyuan 33303, Taiwan.,Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taoyuan 33303, Taiwan
| | - Chih-Jung Chang
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Microbiota Research Center, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Research Center for Emerging Viral Infections, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
| | - Chuan-Sheng Lin
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Microbiota Research Center, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Research Center for Emerging Viral Infections, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
| | - Tsung-Ru Wu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
| | - Ya-Jing Hsu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
| | - Ting-Shu Wu
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Division of Infectious Diseases, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan
| | - Jang-Jih Lu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan
| | - Jan Martel
- Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan
| | - David M Ojcius
- Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94103
| | - Cheng-Lung Ku
- Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Division of Infectious Diseases, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
| | - John D Young
- Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan.,Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan 33305, Taiwan.,Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021; and
| | - Chia-Chen Lu
- Department of Respiratory Therapy, Fu Jen Catholic University, Xinzhuang, New Taipei City 24205, Taiwan
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Abstract
The global spread of non-tuberculous mycobacteria (NTM) may be due to HIV/AIDS and other environmental factors. The symptoms of NTM and tuberculosis (TB) disease are indistinguishable, but their treatments are different. Lack of research on the epidemiology of NTM infections has led to underestimation of its prevalence within TB endemic countries. This study was designed to determine the prevalence and clinical characteristics of pulmonary NTM in Bamako. A cross-sectional study which include 439 suspected cases of pulmonary TB. From 2006 to 2013 a total of 332 (76%) were confirmed to have sputum culture positive for mycobacteria. The prevalence of NTM infection was 9.3% of our study population and 12.3% of culture positive patients. The seroprevalence of HIV in NTM group was 17.1%. Patients who weighed <55 kg and had TB symptoms other than cough were also significantly more likely to have disease due to NTM as compared to those with TB disease who were significantly more likely to have cough and weigh more than 55 kg (OR 0.05 (CI 0.02–0.13) and OR 0.32 (CI 0.11–0.93) respectively). NTM disease burden in Bamako was substantial and diagnostic algorithms for pulmonary disease in TB endemic countries should consider the impact of NTM.
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Cereija TB, Alarico S, Empadinhas N, Pereira PJB. Production, crystallization and structure determination of a mycobacterial glucosylglycerate hydrolase. Acta Crystallogr F Struct Biol Commun 2017; 73:536-540. [PMID: 28876234 PMCID: PMC5619747 DOI: 10.1107/s2053230x17012419] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 08/28/2017] [Indexed: 11/10/2022] Open
Abstract
Glucosylglycerate hydrolase is highly conserved among rapidly growing mycobacteria and has been found to be involved in recovery from nitrogen starvation by promoting the rapid mobilization of the glucosylglycerate that accumulates under these conditions. Here, the production, crystallization and structure determination of glucosylglycerate hydrolase from Mycobacterium hassiacum using two-wavelength anomalous diffraction of selenomethionine-substituted crystals are described. The monoclinic (space group P21) crystals diffracted to ∼2.0 Å resolution at a synchrotron-radiation source and contained four molecules in the asymmetric unit, corresponding to a Matthews coefficient of 3.07 Å3 Da-1 and a solvent content of 59.9%. The quality of the experimental phases allowed the automated building of 1677 of the 1792 residues in the asymmetric unit.
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Affiliation(s)
- Tatiana Barros Cereija
- Biomolecular Structure and Function, IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
- I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal
| | - Susana Alarico
- Molecular Mycobacteriology and Microbiome, CNC – Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal
- III/UC – Instituto de Investigação Interdisciplinar, Universidade de Coimbra, Coimbra, Portugal
| | - Nuno Empadinhas
- Molecular Mycobacteriology and Microbiome, CNC – Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal
- III/UC – Instituto de Investigação Interdisciplinar, Universidade de Coimbra, Coimbra, Portugal
| | - Pedro José Barbosa Pereira
- Biomolecular Structure and Function, IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
- I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
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Martín Asenjo M, Martín Guerra JM, López Pedreira MR, Prieto de Paula JM. Mycobacterium xenopi and squamous cell carcinoma of the lung. Arch Bronconeumol 2017. [PMID: 28641879 DOI: 10.1016/j.arbres.2017.05.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Miguel Martín Asenjo
- Servicio de Medicina Interna, Hospital Clínico Universitario de Valladolid, Valladolid, España.
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33
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Yılmaz N, Uçar EY, Sağlam L. Mycobacterium Tuberculosis and Nontuberculous Mycobacteria Coinfection of the Lungs. Turk Thorac J 2017; 18:23-26. [PMID: 29404154 DOI: 10.5152/turkthoracj.2017.16034] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 10/06/2016] [Indexed: 01/15/2023]
Abstract
Tuberculosis is highly prevalent in our country and nontuberculous mycobacteria (NTM) are frequently found in respiratory specimens recently. A 65-year-old woman was admitted with complaints of fever, cough, weight loss, and hemoptysis. On the patient's chest radiography an upper lobe cavity in both lungs and consolidation was detected. Acid-fast bacilli 4+ were observed in smear of sputum and culture results M. intracellulare and M. tuberculosis were observed together. The patient's treatment was arranged. Through this case, we want to emphasize that tuberculosis and nontuberculous mycobacterial disease can coexist.
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Affiliation(s)
- Nafiye Yılmaz
- Department of Pulmonary Diseases, Ataturk University School of Medicine, Erzurum, Turkey
| | - Elif Yılmazel Uçar
- Department of Pulmonary Diseases, Ataturk University School of Medicine, Erzurum, Turkey
| | - Leyla Sağlam
- Department of Pulmonary Diseases, Ataturk University School of Medicine, Erzurum, Turkey
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34
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Cerna-Cortes JF, Cortes-Cueto AL, Cano-Gaona MR, Leon-Montes N, Helguera-Repetto AC, Rivera-Gutierrez S, Salas-Rangel LP, Castro-Rosas J, Gonzalez-Y-Merchand JA. Microbiological Quality and Occurrence of Nontuberculous Mycobacteria in Fresh-Squeezed Orange Juice Samples Purchased from Street Vendors in Mexico City. J Food Prot 2016; 79:2190-2195. [PMID: 28221956 DOI: 10.4315/0362-028x.jfp-16-197] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Nontuberculous mycobacteria (NTM) are potentially pathogenic agents commonly found in a natural ecosystem. For this reason, food is considered another source of NTM transmission for humans. The aims of this study were to evaluate the microbiological quality and the occurrence of NTM in fresh-squeezed orange juice samples purchased from street vendors. All 102 samples analyzed were positive for aerobic mesophilic bacteria (AMB), with limits ranging from 1.8 to 6.2 log CFU/ml. A total of 55 (54%), 25 (25%), and 13 (13%) orange juice samples were positive for total coliforms (TC), fecal coliforms (FC), and Escherichia coli , respectively. TC, FC, and E. coli were present with limits ranging from <3 to >1,100 most probable number (MPN)/ml, <3 to 460 MPN/ml, and <3 to 11 MPN/ml, respectively. Six orange juice samples harbored NTM. These NTM were identified by using three molecular markers (hsp65, rrs, and rpoB genes) and corresponded to the fast-growing mycobacteria: Mycobacterium fortuitum (n = 3), Mycobacterium rhodesiae (n = 1), Mycobacterium obuense (n = 1), and a mixture of M. fortuitum and Mycobacterium mucogenicum in an additional sample (n = 1). No correlation was found between the presence NTM in orange juice samples with the presence and concentration of the indicator microorganisms (aerobic mesophilic bacteria, TC, and FC). Overall, these results suggest that fresh-squeezed orange juice might represent a vehicle for NTM transmission in humans. Therefore, prevention of contamination by humans (proper handling and washing of oranges) during juice preparation should be recommended.
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Affiliation(s)
- Jorge F Cerna-Cortes
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Ana Laura Cortes-Cueto
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Maria Rosalia Cano-Gaona
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Nancy Leon-Montes
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Addy C Helguera-Repetto
- Departamento de Inmunobioquimica, Torre de Investigación, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales 800, Colonia Lomas de Virreyes, México, D.F., C.P. 11000, Mexico
| | - Sandra Rivera-Gutierrez
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Laura P Salas-Rangel
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
| | - Javier Castro-Rosas
- Centro de Investigaciones Quimicas, Instituto de Ciencias Básicas e Ingenieria, Universidad Autonoma del Estado de Hidalgo, Centro Universitario, Carretera Pachuca-Tulancingo km 4.5, Mineral de la Reforma, Hidalgo, C.P. 42183, México
| | - Jorge A Gonzalez-Y-Merchand
- Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas-Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomas, México, D.F., C.P. 11340, México
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35
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Non-tuberculous mycobacteria: epidemiological pattern in a reference laboratory and risk factors associated with pulmonary disease. Epidemiol Infect 2016; 145:515-522. [PMID: 27804902 DOI: 10.1017/s0950268816002521] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
The diseases caused by non-tuberculous mycobacteria (NTM), in both AIDS and non-AIDS populations, are increasingly recognized worldwide. Although the American Thoracic Society published the guidelines for diagnosis of NTM pulmonary disease (NTM-PD), the diagnosis is still difficult. In the first part of the study, we collected data on NTM isolates in the Mycobacteriology Laboratory of Careggi Hospital (Florence, Italy) and analysed the epidemiological data of NTM isolates. Then, to analyse the risk factors associated to NTM-PD, we studied the presence of ATS/IDSA criteria for NTM-PD in patients who had at least one positive respiratory sample for NTM and were admitted to the Infectious Disease Unit and the Section of Respiratory Medicine. We selected 88 patients with available full clinical data and, according to ATS/IDSA criteria, classified 15 patients (17%) as NTM-PD cases and 73 as colonized patients (83%). When comparing colonized and NTM-PD patients we did not find significant differences of age, gender and comorbidity. We observed that Mycobacterium avium and M. intracellulare were statistically associated with NTM-PD (P = 0·001) whereas M. xenopi was statistically associated with colonization. Although the number of studied patients is limited, our study did not identify risk factors for NTM-PD that could help clinicians to discriminate between colonization and disease. We underline the need of close monitoring of NTM-infected patients until the diagnosis is reasonably excluded. Further larger prospective studies and new biological markers are needed to identify new useful tools for the diagnosis of NTM-PD.
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Dziedzinska R, Makovcova J, Kaevska M, Slany M, Babak V, Moravkova M. Nontuberculous Mycobacteria on Ready-to-Eat, Raw and Frozen Fruits and Vegetables. J Food Prot 2016; 79:1452-6. [PMID: 27497136 DOI: 10.4315/0362-028x.jfp-16-030] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The consumption of fruits and vegetables is increasing worldwide because of the positive impact of these foods on human health. Ready-to-eat, raw whole, and frozen fruits and vegetables were purchased from markets and examined for the presence of nontuberculous mycobacteria (NTM) using culture, real-time PCR (qPCR), and sequencing. Using qPCR, Mycobacterium sp. at 10(0) to 10(4) ge/g (genome equivalents per gram) was found in almost all of the 178 samples; members of the M. avium complex were found only sporadically. Culture and sequencing revealed the presence of 22 viable NTM isolates in 17 samples. In addition to NTM commonly found in the environment, several rarely described isolates of viable NTM were recovered. The presence of Mycobacterium shigaense, which has been previously isolated only from human patients, was found in lettuce, the first time that this species has been found in an environmental sample. Mycobacterium parmense, Mycobacterium palustre, and Mycobacterium llatzerense, which have been previously isolated from human patients and occasionally from soil and water, were recovered from leafy green vegetables. Strawberries and cut salad mixes contained Mycobacterium algericum, Mycobacterium fallax, and Mycobacterium minnesotense. NTM are primarily nonpathogenic. However, consumption of fruits or vegetables contaminated with NTM could represent a health risk for immunocompromised people, children, and the elderly.
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Affiliation(s)
- Radka Dziedzinska
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic
| | - Jitka Makovcova
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic
| | - Marija Kaevska
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic
| | - Michal Slany
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic
| | - Vladimir Babak
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic
| | - Monika Moravkova
- Department of Food and Feed Safety, Veterinary Research Institute, 621 00 Brno, Czech Republic.
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Isolation of Nontuberculous Mycobacteria from the Environment of Ghanian Communities Where Buruli Ulcer Is Endemic. Appl Environ Microbiol 2016; 82:4320-4329. [PMID: 27208141 DOI: 10.1128/aem.01002-16] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 05/04/2016] [Indexed: 12/31/2022] Open
Abstract
UNLABELLED This study aimed to isolate nontuberculous mycobacterial species from environmental samples obtained from some selected communities in Ghana. To optimize decontamination, spiked environmental samples were used to evaluate four decontamination solutions and supplemented media, after which the best decontamination solution and media were used for the actual analysis. The isolates obtained were identified on the basis of specific genetic sequences, including heat shock protein 65, IS2404, IS2606, rpoB, and the ketoreductase gene, as needed. Among the methods evaluated, decontamination with 1 M NaOH followed by 5% oxalic acid gave the highest rate of recovery of mycobacteria (50.0%) and the lowest rate of contamination (15.6%). The cultivation medium that supported the highest rate of recovery of mycobacteria was polymyxin B-amphotericin B-nalidixic acid-trimethoprim-azlocillin-supplemented medium (34.4%), followed by isoniazid-supplemented medium (28.1%). Among the 139 samples cultivated in the main analysis, 58 (41.7%) yielded mycobacterial growth, 70 (50.4%) had no growth, and 11 (7.9%) had all inoculated tubes contaminated. A total of 25 different mycobacterial species were identified. Fifteen species (60%) were slowly growing (e.g., Mycobacterium ulcerans, Mycobacterium avium, Mycobacterium mantenii, and Mycobacterium malmoense), and 10 (40%) were rapidly growing (e.g., Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium abscessus). The occurrence of mycobacterial species in the various environmental samples analyzed was as follows: soil, 16 species (43.2%); vegetation, 14 species (38.0%); water, 3 species (8.0%); moss, 2 species (5.4%); snail, 1 species (2.7%); fungi, 1 species (2.7%). This study is the first to report on the isolation of M. ulcerans and other medically relevant nontuberculous mycobacteria from different environmental sources in Ghana. IMPORTANCE Diseases caused by mycobacterial species other than those that cause tuberculosis and leprosy are increasing. Control is difficult because the current understanding of how the organisms are spread and where they live in the environment is limited, although this information is needed to design preventive measures. Growing these organisms from the environment is also difficult, because the culture medium becomes overgrown with other bacteria that also live in the environment, such as in soil and water. We aimed to improve the methods for growing these organisms from environmental sources, such as soil and water samples, for better understanding of important mycobacterial ecology.
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Stanish LF, Hull NM, Robertson CE, Harris JK, Stevens MJ, Spear JR, Pace NR. Factors Influencing Bacterial Diversity and Community Composition in Municipal Drinking Waters in the Ohio River Basin, USA. PLoS One 2016; 11:e0157966. [PMID: 27362708 PMCID: PMC4928833 DOI: 10.1371/journal.pone.0157966] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 06/08/2016] [Indexed: 12/29/2022] Open
Abstract
The composition and metabolic activities of microbes in drinking water distribution systems can affect water quality and distribution system integrity. In order to understand regional variations in drinking water microbiology in the upper Ohio River watershed, the chemical and microbiological constituents of 17 municipal distribution systems were assessed. While sporadic variations were observed, the microbial diversity was generally dominated by fewer than 10 taxa, and was driven by the amount of disinfectant residual in the water. Overall, Mycobacterium spp. (Actinobacteria), MLE1-12 (phylum Cyanobacteria), Methylobacterium spp., and sphingomonads were the dominant taxa. Shifts in community composition from Alphaproteobacteria and Betaproteobacteria to Firmicutes and Gammaproteobacteria were associated with higher residual chlorine. Alpha- and beta-diversity were higher in systems with higher chlorine loads, which may reflect changes in the ecological processes structuring the communities under different levels of oxidative stress. These results expand the assessment of microbial diversity in municipal distribution systems and demonstrate the value of considering ecological theory to understand the processes controlling microbial makeup. Such understanding may inform the management of municipal drinking water resources.
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Affiliation(s)
- Lee F. Stanish
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, United States of America
- * E-mail:
| | - Natalie M. Hull
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, United States of America
| | - Charles E. Robertson
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, United States of America
| | - J. Kirk Harris
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Mark J. Stevens
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - John R. Spear
- Department of Civil and Environmental Engineering, Colorado School of Mines, Golden, CO, United States of America
| | - Norman R. Pace
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, United States of America
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General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection. J Pathog 2015; 2015:809014. [PMID: 26618006 PMCID: PMC4649093 DOI: 10.1155/2015/809014] [Citation(s) in RCA: 82] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 10/15/2015] [Indexed: 11/17/2022] Open
Abstract
Nontuberculous mycobacteria (NTM) are emergent pathogens whose importance in human health has been growing. After being regarded mainly as etiological agents of opportunist infections in HIV patients, they have also been recognized as etiological agents of several infections on immune-competent individuals and healthcare-associated infections. The environmental nature of NTM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis. Here, we review the clinical manifestations attributed to NTM giving particular importance to the role played by biofilm assembly.
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40
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Guglielmetti L, Mougari F, Lopes A, Raskine L, Cambau E. Human infections due to nontuberculous mycobacteria: the infectious diseases and clinical microbiology specialists' point of view. Future Microbiol 2015; 10:1467-83. [PMID: 26344005 DOI: 10.2217/fmb.15.64] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Nontuberculous mycobacteria (>150 species such as Mycobacterium avium, Mycobacterium kansasii, Mycobacterium chelonae and Mycobacterium abscessus) are opportunistic pathogens causing lung and extrarespiratory infections, beside M. ulcerans and M. marinum that are pathogens causing specific skin and soft tissue infections. Disseminated infections occur only in severe immunosuppressed conditions such as AIDS. The diagnosis is based on repeated isolations of the same mycobacterium associated with clinical and radiological signs, and the absence of tuberculosis. Precise species identification is obtained by molecular biology. Therapeutic antibiotic regimens differ with regard to the mycobacterial species that are involved. Prevention of iatrogenic infections relies on using sterile water in all injections, healthcare and cosmetic occupations. Future perspectives are to set effective antibiotic regimens tested in randomized therapeutic trials.
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Affiliation(s)
- Lorenzo Guglielmetti
- AP-HP, Hôpital Lariboisière-Fernand Widal, Service de Bactériologie, F-75010 Paris, France.,Centre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), F-75010 Paris, France.,Service de Maladies Infectieuses, Hôpital de Verona, Italie
| | - Faiza Mougari
- AP-HP, Hôpital Lariboisière-Fernand Widal, Service de Bactériologie, F-75010 Paris, France.,Centre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), F-75010 Paris, France.,IAME, UMR 1137, INSERM, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France
| | - Amanda Lopes
- AP-HP, Hôpital Lariboisière-Fernand Widal, Service de Médecine interne 1, F-75475 Paris, France
| | - Laurent Raskine
- AP-HP, Hôpital Lariboisière-Fernand Widal, Service de Bactériologie, F-75010 Paris, France.,Centre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), F-75010 Paris, France
| | - Emmanuelle Cambau
- AP-HP, Hôpital Lariboisière-Fernand Widal, Service de Bactériologie, F-75010 Paris, France.,Centre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), F-75010 Paris, France.,IAME, UMR 1137, INSERM, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France
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Affiliation(s)
- J. S. Weese
- Department of Pathobiology; Ontario Veterinary College; University of Guelph; Canada
| | - D. Gomez-Nieto
- Department of Pathobiology; Ontario Veterinary College; University of Guelph; Canada
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Kotilainen H, Valtonen V, Tukiainen P, Poussa T, Eskola J, Järvinen A. Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria. Eur J Clin Microbiol Infect Dis 2015; 34:1909-18. [PMID: 26155783 PMCID: PMC4545189 DOI: 10.1007/s10096-015-2432-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 06/17/2015] [Indexed: 01/11/2023]
Abstract
We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33–0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31–0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25–0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9–20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4–5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05–5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04–1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24–0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.
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Affiliation(s)
- H Kotilainen
- University of Helsinki and Division of Infectious Diseases, Inflammation Center, Department of Medicine, Helsinki University Hospital, Helsinki, Finland,
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Wang J, Wang Z, Yao Y, Wu J, Tang X, Gu T, Li G. The fibroblast growth factor-2 arrests Mycobacterium avium sp. paratuberculosis growth and immunomodulates host response in macrophages. Tuberculosis (Edinb) 2015; 95:505-14. [DOI: 10.1016/j.tube.2015.04.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 03/28/2015] [Accepted: 04/08/2015] [Indexed: 10/23/2022]
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Nasiri MJ, Dabiri H, Darban-Sarokhalil D, Hashemi Shahraki A. Prevalence of Non-Tuberculosis Mycobacterial Infections among Tuberculosis Suspects in Iran: Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0129073. [PMID: 26052701 PMCID: PMC4460155 DOI: 10.1371/journal.pone.0129073] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Accepted: 05/04/2015] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION The infections due to Non-Tuberculosis Mycobacteria (NTM) are becoming an important health problem in many countries in the world. Globally, an increase in NTM infections has been reported from many countries around the world. However, limited information is available about the prevalence of NTM infections in Iran. MATERIAL AND METHODS The data of the prevalence of NTM infections were collected from databases such as PubMed, Web of science, Cochrane Library, Embase, Scopus, Iranmedex, and Scientific Information Database. Comprehensive Meta-Analysis (V2.0, Biostat) software was used to analyze the data. RESULTS The meta-analyses showed that the prevalence of NTM infections was 10.2% (95% confidence interval [95% CI] 6.3-15.9) among culture-positive cases of tuberculosis (TB) in Iran. The further stratified analyses indicated that the prevalence of NTM was higher in studies that were done after year 2000. Additionally, M. simiae (43.3% [95% CI 36.8-50.0]), M. intracellucar (27.3% [95% CI 0.7-95.5]) and M. fortuitum (22.7% [95% CI 16.1-30.9]) were the most prevalent NTM species, respectively. DISCUSSION The relatively high prevalence of NTM infections (10.2%) among culture positive cases for TB underlines the need for greater enforcement of infection control strategies. Establishment of appropriate diagnostic criteria and management guidelines for NTM diseases and expanding the number and quality of regional reference laboratories may facilitate more accurate action for prevention and control of NTM infections in Iran.
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Affiliation(s)
- Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- * E-mail:
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Hernández-Toloza JE, Rincón-Serrano MDP, Celis-Bustos YA, Aguillón CI. [Identification of mycobacteria to the species level by molecular methods in the Public Health Laboratory of Bogotá, Colombia]. Enferm Infecc Microbiol Clin 2015; 34:17-22. [PMID: 25888362 DOI: 10.1016/j.eimc.2015.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 02/27/2015] [Accepted: 03/02/2015] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Global epidemiology of non-tuberculous mycobacteria (NTM) is unknown due to the fact that notification is not required in many countries, however the number of infection reports and outbreaks caused by NTM suggest a significant increase in the last years. Traditionally, mycobacteria identification is made through biochemical profiles which allow to differentiate M. tuberculosis from NTM, and in some cases the mycobacteria species. Nevertheless, these methods are technically cumbersome and time consuming. On the other hand, the introduction of methods based on molecular biology has improved the laboratory diagnosis of NTM. OBJECTIVE To establish the NTM frequency in positive cultures for acid-fast bacilli (AAFB) which were sent to Laboratorio de Salud Pública de Bogotá over a 12 month period. MATERIALS AND METHODS A total of 100 positive cultures for acid-fast bacilli from public and private hospitals from Bogotá were identified by both biochemical methods and the molecular methods PRA (PCR-restriction enzyme analysis) and multiplex-PCR. Furthermore, low prevalence mycobacteria species and non-interpretable results were confirmed by 16SrDNA sequentiation analysis. RESULTS Identification using the PRA method showed NMT occurrence in 11% of cultures. In addition, this molecular methodology allowed to detect the occurrence of more than one mycobacteria in 4% of the cultures. Interestingly, a new M. kubicae pattern of PCR-restriction analysis is reported in our study. CONCLUSION Using a mycobacteria identification algorithm, which includes the molecular method PRA, improves the diagnostic power of conventional methods and could help to advance both NTM epidemiology knowledge and mycobacteriosis control.
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Microbiological Quality of Ready-to-Eat Vegetables Collected in Mexico City: Occurrence of Aerobic-Mesophilic Bacteria, Fecal Coliforms, and Potentially Pathogenic Nontuberculous Mycobacteria. BIOMED RESEARCH INTERNATIONAL 2015; 2015:789508. [PMID: 25918721 PMCID: PMC4396000 DOI: 10.1155/2015/789508] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 09/24/2014] [Indexed: 01/08/2023]
Abstract
The aims of this study were to evaluate the microbiological quality and the occurrence of nontuberculous mycobacteria (NTM) in a variety of salads and sprouts from supermarkets and street vendors in Mexico City. Aerobic-mesophilic bacteria (AMB) were present in 100% of RTE-salads samples; 59% of samples were outside guidelines range (>5.17 log10 CFU per g). Although fecal coliforms (FC) were present in 32% of samples, only 8% of them exceeded the permissible limit (100 MPN/g). Regarding the 100 RTE-sprouts, all samples were also positive for AMB and total coliforms (TC) and 69% for FC. Seven NTM species were recovered from 7 salad samples; they included three M. fortuitum, two M. chelonae, one M. mucogenicum, and one M. sp. Twelve RTE-sprouts samples harbored NTM, which were identified as M. porcinum (five), M. abscessus (two), M. gordonae (two), M. mucogenicum (two), and M. avium complex (one). Most RTE-salads and RTE-sprouts had unsatisfactory microbiological quality and some harbored NTM associated with illness. No correlation between the presence of coliforms and NTM was found. Overall, these results suggest that RTE-salads and RTE-sprouts might function as vehicles for NTM transmission in humans; hence, proper handling and treatment before consumption of such products might be recommendable.
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Evaluation of the inflammatory response in macrophages stimulated with exosomes secreted by Mycobacterium avium-infected macrophages. BIOMED RESEARCH INTERNATIONAL 2015; 2015:658421. [PMID: 25861639 PMCID: PMC4378337 DOI: 10.1155/2015/658421] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 03/04/2015] [Accepted: 03/04/2015] [Indexed: 11/29/2022]
Abstract
Exosomes secreted from Mycobacterium avium-infected macrophages contain numerous antigens of both M. avium and the host cell and are involved in the induction and expression of the inflammatory responses in macrophages. The interaction between exosomes secreted from M. avium-infected macrophages and macrophage phagocytosis, cytokine secretion, immunostimulation, and apoptosis was analyzed. Upon stimulation with exosomes secreted from M. avium-infected macrophages, the phagocytosis of dextran by treated macrophages was increased. Furthermore, the expression of CD40, CD80, CD81, CD86, HLA-DR, and most notably CD195 was enhanced. Additionally, the secretion of IL-6, IL-8, IL-10, IFN-γ, and TNF-α was increased by stimulated macrophages. Exosome stimulation did not induce macrophage apoptosis when compared with macrophages infected with M. avium. Caspase expression, including that of caspases 3, 6, and 8, was also not altered in exosome stimulated macrophages. Thus exosomes trigger the inflammatory response in macrophages owing to the presence of bacterial antigens but have no effect on macrophage viability.
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Bacteriological and virulence study of a Mycobacterium chimaera isolate from a patient in China. Antonie van Leeuwenhoek 2015; 107:901-9. [DOI: 10.1007/s10482-015-0382-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 01/09/2015] [Indexed: 01/15/2023]
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García-Martos P, García-Agudo L, González-Moya E, Galán F, Rodríguez-Iglesias M. [Infections due to Mycobacterium simiae]. Enferm Infecc Microbiol Clin 2014; 33:e37-43. [PMID: 25444043 DOI: 10.1016/j.eimc.2014.07.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 05/26/2014] [Accepted: 07/22/2014] [Indexed: 10/24/2022]
Abstract
Mycobacterium simiae is a slow-growing photochromogenic environmental mycobacterium, first described in 1965. Rarely associated with human infections, possibly due to its limited pathogenicity, it mainly produces lung infection in immunocompetent elderly patients with underlying lung disease, and in disseminated infections in immunosuppressed young patients with AIDS. A microbiological culture is needed to confirm the clinical suspicion, and genetic sequencing techniques are essential to correctly identify the species. Treating M. simiae infections is complicated, owing to the multiple resistance to tuberculous drugs and the lack of correlation between in vitro susceptibility data and in vivo response. Proper treatment is yet to be defined, but must include clarithromycin combined with other antimicrobials such as moxifloxacin and cotrimoxazole. It is possible that M. simiae infections are undiagnosed.
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Affiliation(s)
| | | | | | - Fátima Galán
- Servicio de Microbiología, Hospital Puerta del Mar, Cádiz, España
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50
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Kim JJ, Lee J, Jeong SY. Mycobacterium szulgai pulmonary infection: case report of an uncommon pathogen in Korea. Korean J Radiol 2014; 15:651-4. [PMID: 25246828 PMCID: PMC4170168 DOI: 10.3348/kjr.2014.15.5.651] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 06/22/2014] [Indexed: 11/15/2022] Open
Abstract
Mycobacterium szulgai (M. szulgai) is an unusual pathogen in a human non-tuberculous mycobacterial infection. Pulmonary infection due to M. szulgai may be clinically and radiologically confused with active pulmonary tuberculosis. In contrast to other non-tuberculous mycobacteria, M. szulgai infection is well controlled by combination antimycobacterial therapy. Most of the previously reported cases of M. szulgai pulmonary infection showed cavitary upper lobe infiltrates. We herein describe a case of pulmonary M. szulgai infection that shows clinical and radiological presentations similar to active pulmonary tuberculosis.
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Affiliation(s)
- Jeong Jae Kim
- Department of Radiology, Jeju National University School of Medicine, Jeju 690-767, Korea
| | - Jaechun Lee
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju 690-767, Korea
| | - Sun Young Jeong
- Department of Radiology, Jeju National University School of Medicine, Jeju 690-767, Korea
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