• Crohn’s disease
• Goblet cells
• Inflammatory bowel disease
• Intestinal epithelial cells

• BSZK-2023-Z06 the Most Important Discipline, Baoshan Medical Key Discipline and Characteristic Brand Construction Project
• 2023-E-13 2022 Baoshan Medical and Health Project
• RJPY-LX-004 Cultivation Funding for Clinical Scientific Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University
• 2023-rbcxjj-001 Clinical Scientific Research and Innovation Cultivation Fund Project, Baoshan Branch, Renji Hospital, Shanghai Jiao Tong University School of Medicine
• the Most Important Discipline, Baoshan Medical Key Discipline and Characteristic Brand Construction Project

• cell biology
• microbiology

• L. monocytogenes
• host infection
• listeriosis
• molecular mechanisms
• virulence traits

Listeria monocytogenes is an important foodborne pathogen which has the ability to adapt and survive in food and food processing facilities where it can persist for years. In this study, a total of 143 L. monocytogenes isolates in South Africa (SA) were characterized for their strain’s genetic relatedness, virulence profiles, stress tolerance and resistance genes associated with L. monocytogenes. The Core Genome Multilocus Sequence Typing (cgMLST) analysis revealed that the most frequent serogroups were IVb and IIa; Sequence Types (ST) were ST204, ST2, and ST1; and Clonal Complexes (CC) were CC204, CC1, and CC2. Examination of genes involved in adaptation and survival of L. monocytogenes in SA showed that ST1, ST2, ST121, ST204, and ST321 are well adapted in food processing environments due to the significant over-representation of Benzalkonium chloride (BC) resistance genes (bcrABC cassette, ermC, mdrL and Ide), stress tolerance genes (SSI-1 and SSI-2), Prophage (φ) profiles (LP_101, vB LmoS 188, vB_LmoS_293, and B054 phage), plasmids profiles (N1-011A, J1776, and pLM5578) and biofilm formation associated genes. Furthermore, the L. monocytogenes strains that showed hyper-virulent potential were ST1, ST2 and ST204, and hypo-virulent were ST121 and ST321 because of the presence and absence of major virulence factors such as LIPI-1, LIPI-3, LIPI-4 and the internalin gene family members including inlABCEFJ. The information provided in this study revealed that hyper-virulent strains ST1, ST2, and ST204 could present a major public health risk due to their association with meat products and food processing environments in SA.

• AMR
• Benzalkonium chloride resistance
• cgMLST
• cgSNP
• plasmids
• prophages
• stress tolerance
• virulence profiles

Early diagnosis and appropriate antibiotic treatment are important to survival of Listeria monocytogenes (L. monocytogenes) bacteremia. Penicillin tends to be the most commonly used antibiotic. However, there are limited data on antibiotic use in elderly patients with serious complications. We describe the clinical presentation, antibiotic therapy, and traceability of L. monocytogenes in a centenarian with a history of eating frozen food.

A 102-year-old man suffered from high fever with chill after hematochezia. Tentative diagnoses were lower gastrointestinal hemorrhage and localized peritonitis. Meropenem and ornidazole were the empirical therapy. The patient did not respond and developed multiple system dysfunction even after teicoplanin was added to the therapy. L. monocytogenes was identified from blood cultures on day 5 of admission. The patient had a history of consuming frozen dumplings. Meropenem/ornidazole/teicoplanin were replaced with meropenem/linezolid. The patient gradually became afebrile. He received meropenem/linezolid for 10 d, and piperacillin/tazobactam was applied as step-down treatment for 2 wk with good clinical results. There was no sign of relapse during follow-up after discharge. L. monocytogenes isolates from the patient and frozen dumplings belonged to different serotypes and sequence types (STs): 1/2b and ST5 from the patient and 1/2c and ST9 from the dumplings.

More awareness of listeriosis should be raised. Linezolid might be an option for listeriosis in elderly people with serious complications.

• Listeria monocytogenes
• Centenarian
• Bacteremia
• Traceability
• Antibiotics
• Case report

Trillions of microbes exist in the human body, particularly the gastrointestinal tract, coevolved with the host in a mutually beneficial relationship. The main role of the intestinal microbiome is the fermentation of non-digestible substrates and increased growth of beneficial microbes that produce key antimicrobial metabolites such as short-chain fatty acids, etc., to inhibit the growth of pathogenic microbes besides other functions. Intestinal microbiota can prevent pathogen colonization through the mechanism of colonization resistance. A wide range of resistomes are present in both beneficial and pathogenic microbes. Giving antibiotic exposure to the intestinal microbiome (both beneficial and hostile) can trigger a resistome response, affecting colonization resistance. The following review provides a mechanistic overview of the intestinal microbiome and the impacts of antibiotic therapy on pathogen colonization and diseases. Further, we also discuss the epidemiology of immunocompromised patients who are at high risk for nosocomial infections, colonization and decolonization of multi-drug resistant organisms in the intestine, and the direct and indirect mechanisms that govern colonization resistance to the pathogens.

• antibiotics
• colonization resistance
• diseases
• intestinal microbiota
• pathogens

• Animals
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use
• Anti-Infective Agents/pharmacology
• Anti-Infective Agents/therapeutic use
• Antibiosis
• Antimicrobial Cationic Peptides/pharmacology
• Antimicrobial Cationic Peptides/therapeutic use
• Cross Infection/drug therapy
• Cross Infection/etiology
• Disease Susceptibility
• Drug Resistance, Multiple
• Gastrointestinal Microbiome/drug effects
• Host-Pathogen Interactions
• Humans
• Sepsis/etiology

• Listeria monocytogenes
• antibodies
• antigens
• detection
• lateral flow immunoassay
• listeriosis
• pathogenesis
• serological methods
• virulence

• H. pylori
• AI-2
• LuxS
• inflammatory response
• quorum sensing

• Listeria monocytogenes
• Muc2
• dissemination
• population dynamics

• Intestinal diseases
• Intestinal microbiota
• MUC2 mucin

Gut organoids are stem cell derived 3D models of the intestinal epithelium that are useful for studying interactions between enteric pathogens and their host. While the organoid model has been used for both bacterial and viral infections, this is a closed system with the luminal side being inaccessible without microinjection or disruption of the organoid polarization. In order to overcome this and simplify their applicability for transepithelial studies, permeable membrane based monolayer approaches are needed. In this paper, we demonstrate a method for generating a monolayer model of the human fetal intestinal polarized epithelium that is fully characterized and validated. Proximal and distal small intestinal organoids were used to generate 2D monolayer cultures, which were characterized with respect to epithelial cell types, polarization, barrier function, and gene expression. In addition, viral replication and bacterial translocation after apical infection with enteric pathogens Enterovirus A71 and Listeria monocytogenes were evaluated, with subsequent monitoring of the pro-inflammatory host response. This human 2D fetal intestinal monolayer model will be a valuable tool to study host-pathogen interactions and potentially reduce the use of animals in research.

• enteric pathogens
• gut barrier
• host-pathogen interactions
• human organoids
• polarized epithelium
• small intestine

Although it rarely induces disease in humans, Listeria monocytogenes (Lm) is important due to the frequency of serious pathological conditions—such as sepsis and meningitis—it causes in those few people that do get infected. Virulence factors (VF) of Lm—especially those involved in the passage through multiple cellular barriers of the body, including internalin (Inl) family members and listeriolysin O (LLO)—have been investigated both in vitro and in vivo, but the majority of work was focused on the mechanisms utilized during penetration of the gut and fetoplacental barriers. The role of listerial VF during entry into other organs remain as only partially solved puzzles. Here, we review the current knowledge on the entry of Lm into one of its more significant destinations, the brain, with a specific focus on the role of various VF in cellular adhesion and invasion.

• Listeria monocytogenes
• autolysin
• brain invasion
• internalin
• listeriolysin
• virulence factors

• bacterial enteric infection
• bacteriocins
• bacteriophages
• bile acids
• colonization resistance
• enteric pathogens
• gut microbiota
• microbiome
• mucus layer
• nutrient competition
• short-chain fatty acids

• Animals
• Anti-Infective Agents/pharmacology
• Bacteria/metabolism
• Bacteria/pathogenicity
• Bacterial Infections/microbiology
• Fatty Acids, Volatile/biosynthesis
• Gastrointestinal Microbiome
• Humans
• Mice
• Mucus

• R01 GM099514 NIGMS NIH HHS
• R25 GM116149 NIGMS NIH HHS
• U54 CK000607 NCEZID CDC HHS
• U54 CK000481 NCEZID CDC HHS
• U01 AI124255 NIAID NIH HHS
• Royal Society Wolfson Research Merit Award
• Vedanta Biosciences Inc.
• HHS | National Institutes of Health (NIH)

• Listeria adhesion protein (LAP)
• Listeria monocytogenes
• food safety
• foodborne infection
• internalin A (InlA)
• intestinal epithelial barrier crossing
• myosin light-chain kinase (MLCK)
• nuclear factor κB (NF-κB);

• Animals
• Bacterial Adhesion
• Bacterial Proteins/metabolism
• Bacterial Translocation
• Cadherins/metabolism
• Food Safety
• Foodborne Diseases/microbiology
• Foodborne Diseases/prevention & control
• Host-Pathogen Interactions/immunology
• Humans
• Intestinal Mucosa/cytology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Listeria monocytogenes/metabolism
• Listeria monocytogenes/pathogenicity

• food processing
• gut
• human pathogen
• immunity
• infection
• pathogen survival
• pathogenesis
• stress response and adaptation

• O-glycosylation
• bacteria
• farm animal
• host-pathogen interaction
• intestine
• mucin
• mucus
• parasite
• stomach

• Candida albicans
• Porphyromonas gingivalis
• RNA-Seq
• microbial communities
• polymicrobial synergy

Listeria monocytogenes is a foodborne pathogen that can cause febrile gastroenteritis in healthy subjects and systemic infections in immunocompromised individuals. Despite the high prevalence of L. monocytogenes in the environment and frequent contamination of uncooked meat and poultry products, infections with this pathogen are relatively uncommon, suggesting that protective defenses in the general population are effective. In the mammalian gastrointestinal tract, a variety of defense mechanisms prevent L. monocytogenes growth, epithelial penetration and systemic dissemination. Among these defenses, colonization resistance mediated by the gut microbiota is crucial in protection against a range of intestinal pathogens, including L. monocytogenes. Here we review defined mechanisms of defense against L. monocytogenes in the lumen of the gastro-intestinal tract, with particular emphasis on protection conferred by the autochthonous microbiota. We suggest that selected probiotic species derived from the microbiota may be developed for eventual clinical use to enhance resistance against L. monocytogenes infections.

• Listeria monocytogenes
• colonization resistance
• microbiota

Porphyromonas gingivalis is an important cause of serious periodontal diseases, and is emerging as a pathogen in several systemic conditions including some forms of cancer. Initial colonization by P. gingivalis involves interaction with gingival epithelial cells, and the organism can also access host tissues and spread haematogenously. To better understand the mechanisms underlying these properties, we utilized a highly saturated transposon insertion library of P. gingivalis, and assessed the fitness of mutants during epithelial cell colonization and survival in a murine abscess model by high-throughput sequencing (Tn-Seq). Transposon insertions in many genes previously suspected as contributing to virulence showed significant fitness defects in both screening assays. In addition, a number of genes not previously associated with P. gingivalis virulence were identified as important for fitness. We further examined fitness defects of four such genes by generating defined mutations. Genes encoding a carbamoyl phosphate synthetase, a replication-associated recombination protein, a nitrosative stress responsive HcpR transcription regulator, and RNase Z, a zinc phosphodiesterase, showed a fitness phenotype in epithelial cell colonization and in a competitive abscess infection. This study verifies the importance of several well-characterized putative virulence factors of P. gingivalis and identifies novel fitness determinants of the organism.

• Tn-Seq
• fitness
• oral
• pathogenicity
• periodontal

• Listeria monocytogenes
• biofilm
• food industry
• inhibition
• pathogen

The food-borne pathogen Listeria (L.) monocytogenes is able to survive for months and even years in food production environments. Strains belonging to sequence type (ST)121 are particularly found to be abundant and to persist in food and food production environments. To elucidate genetic determinants characteristic for L. monocytogenes ST121, we sequenced the genomes of 14 ST121 strains and compared them with currently available L. monocytogenes ST121 genomes. In total, we analyzed 70 ST121 genomes deriving from 16 different countries, different years of isolation, and different origins—including food, animal and human ST121 isolates. All ST121 genomes show a high degree of conservation sharing at least 99.7% average nucleotide identity. The main differences between the strains were found in prophage content and prophage conservation. We also detected distinct highly conserved subtypes of prophages inserted at the same genomic locus. While some of the prophages showed more than 99.9% similarity between strains from different sources and years, other prophages showed a higher level of diversity. 81.4% of the strains harbored virtually identical plasmids. 97.1% of the ST121 strains contain a truncated internalin A (inlA) gene. Only one of the seven human ST121 isolates encodes a full-length inlA gene, illustrating the need of better understanding their survival and virulence mechanisms.

• Genome, Bacterial
• Humans
• Listeria monocytogenes/classification
• Listeria monocytogenes/genetics
• Listeria monocytogenes/pathogenicity
• Plasmids
• Virulence/genetics

• P 27920 Austrian Science Fund FWF
• Austrian Science Fund
• USDA National Institute of Food and Agriculture

The bacterial etiological agent of listeriosis, Listeria monocytogenes, is an opportunistic intracellular foodborne pathogen. The infection cycle of L. monocytogenes is well-characterized and involves several key virulence factors, including internalins A and B. While 35 genes encoding internalins have been identified in L. monocytogenes, less than half of them have been characterized as yet. Focusing on lmo2026, it was shown this gene encodes a class I internalin, InlL, exhibiting domains potentially involved in adhesion. Following a functional genetic approach, InlL was demonstrated to be involved in initial bacterial adhesion as well as sessile development in L. monocytogenes. In addition, InlL enables binding to mucin of type 2, i.e., the main secreted mucin making up the mucus layer, rather than to surface-located mucin of type 1. InlL thus appears as a new molecular determinant contributing to the colonization ability of L. monocytogenes.

• Listeria monocytogenes
• bacterial adhesion
• biofilm formation
• cell-surface protein
• internalin
• mucins

Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by T_H2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong T_H2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection.

Approximately 2 billion people are infected with worms every year, causing physical, nutritional and cognitive impairment particularly in children. Mucins are large sugar-coated (glycosylated) proteins that form the intestinal mucus layer. This mucus layer protects our ‘insides’ from external insults and plays an important role during worm infection. We discovered that there is a difference in the glycosylation of mucins in people infected with worms compared to uninfected individuals. Therefore, using different mouse models we investigated the role of glycosylation, and in particular sulphation of mucins in infection. We found that mucin glycosylation is controlled by the immune response and increased sulphation correlated with the expulsion of the worm from the host. Highly sulphated mucins were protected from degradation by the worm. Moreover, mice lacking a sulphate transporter had significantly lower sulphation levels on mucins, which resulted in a reduction in the establishment of the worms and chronic infection.

• Animals
• Disease Models, Animal
• Glycosylation
• Goblet Cells/chemistry
• Goblet Cells/immunology
• Humans
• Immunohistochemistry
• Intestinal Mucosa/chemistry
• Intestinal Mucosa/immunology
• Mice
• Mice, Inbred AKR
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• Mucins/chemistry
• Mucins/immunology
• Polymerase Chain Reaction
• Trichuriasis/immunology
• Trichuris/immunology

• Biotechnology and Biological Sciences Research Council
• WT100290MA Wellcome Trust
• 088785/Z/09/Z Wellcome Trust
• University of Queensland
• National Health and Medical Research Council
• Mater Foundation

Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have. Binding of H. pylori to Le^b-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Le^b. Furthermore, deletion of arsS lead to a decrease in binding to Le^b-glycoconjugates and Le^b-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Le^b-glycoconjugates. Inhibition of proliferation caused by adhesin dependent binding to mucins, and the subsequent aggregation suggests a new role of mucins in the host defense against H. pylori. This aggregating trait of mucins may be useful to incorporate into the design of adhesin inhibitors and other disease intervention molecules.

Resistance emergence against antileishmanial drugs, particularly Sodium Antimony Gluconate (SAG) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. Cysteine leucine rich protein (CLrP), was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of L. donovani. The present study deals with the characterization of CLrP and for its possible connection with SAG resistance.

In pursuance of deciphering the role of CLrP in SAG resistance, gene was cloned, over-expressed in E. coli system and thereafter antibody was raised. The expression profile of CLrP and was found to be over-expressed in SAG resistant clinical isolates of L. donovani as compared to SAG sensitive ones when investigated by real-time PCR and western blotting. CLrP has been characterized through bioinformatics, immunoblotting and immunolocalization analysis, which reveals its post-translational modification along with its dual existence in the nucleus as well as in the membrane of the parasite. Further investigation using a ChIP assay confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate of L. donovani significantly decreased its responsiveness to SAG (SbV and SbIII) and a shift towards the resistant mode was observed. Further, a significant increase in its infectivity in murine macrophages has been observed.

The study reports the differential expression of CLrP in SAG sensitive and resistant isolates of L. donovani. Functional intricacy of CLrP increases with dual localization, glycosylation and DNA binding potential of the protein. Further over-expressing CLrP in sensitive isolate of L. donovani shows significantly decreased sensitivity towards SAG and increased infectivity as well, thus assisting the parasite in securing a safe niche. Results indicates the possible contribution of CLrP to antimonial resistance in L. donovani by assisting the parasite growth in the macrophages.

Leishmania causes complex of pathologies called Leishmaniasis and among the several forms visceral leishmaniasis is the precarious one as being fatal, if left untreated. Emergence of resistance against several antileishmanials particularly Sodium Antimony Gluconate (SAG) has severely battered the therapeutic strategy against VL and the resistance mechanism is still vague. Thus, to apprehend the underlying mechanism, previously, a differential proteomics of SAG unresponsive versus SAG sensitive isolates of L.donovani was done wherein overexpression of Cysteine Leucine Rich protein (CLrP), a member of Leucine rich repeat superfamily, was observed. To scrutinize its involvement in the SAG resistance mechanism, which is till date not investigated, the characterization of CLrP was carried out which revealed its post-translational modification along with its dual existence in the nucleus and in the membrane of the parasite. Further investigation using a ChIP assay confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate of L. donovani significantly decreased its SAG sensitivity. CLrP overexpressed parasites have increased infectivity. These results point out towards the CLrP’s contribution to antimonial resistance in L. donovani by facilitating parasites growth through macrophages. Further studies are required to depict CLrP as a potential drug target to strengthen the present arsenal against L donovani.

• Antibodies, Protozoan
• Antimony/pharmacology
• Antiprotozoal Agents/pharmacology
• Cloning, Molecular
• DNA, Protozoan/genetics
• Drug Resistance
• Escherichia coli
• Gene Expression Regulation
• Genome, Protozoan
• Leishmania donovani/drug effects
• Leishmania donovani/genetics
• Leishmania donovani/metabolism
• Phylogeny
• Protozoan Proteins/genetics
• Protozoan Proteins/metabolism

• Lactobacillus rhamnosus
• bacterial adhesion
• extracellular matrix (ECM) proteins
• mucus-binding factor

• Invasion
• LPXTG protein
• Listeria
• Lmo1413
• Mucin

Listeria monocytogenes is a food-borne pathogen that causes infections with a high-mortality rate and has served as an invaluable model for intracellular parasitism. Here, we report complete genome sequences for two L. monocytogenes strains belonging to serotype 4a (L99) and 4b (CLIP80459), and transcriptomes of representative strains from lineages I, II, and III, thereby permitting in-depth comparison of genome- and transcriptome -based data from three lineages of L. monocytogenes. Lineage III, represented by the 4a L99 genome is known to contain strains less virulent for humans.

The genome analysis of the weakly pathogenic L99 serotype 4a provides extensive evidence of virulence gene decay, including loss of several important surface proteins. The 4b CLIP80459 genome, unlike the previously sequenced 4b F2365 genome harbours an intact inlB invasion gene. These lineage I strains are characterized by the lack of prophage genes, as they share only a single prophage locus with other L. monocytogenes genomes 1/2a EGD-e and 4a L99. Comparative transcriptome analysis during intracellular growth uncovered adaptive expression level differences in lineages I, II and III of Listeria, notable amongst which was a strong intracellular induction of flagellar genes in strain 4a L99 compared to the other lineages. Furthermore, extensive differences between strains are manifest at levels of metabolic flux control and phosphorylated sugar uptake. Intriguingly, prophage gene expression was found to be a hallmark of intracellular gene expression. Deletion mutants in the single shared prophage locus of lineage II strain EGD-e 1/2a, the lma operon, revealed severe attenuation of virulence in a murine infection model.

Comparative genomics and transcriptome analysis of L. monocytogenes strains from three lineages implicate prophage genes in intracellular adaptation and indicate that gene loss and decay may have led to the emergence of attenuated lineages.

microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (ΔinlAB or Δhly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR- 146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following ΔinlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization.

• Caco-2
• Listeria monocytogenes
• epithelial cells
• infection
• microRNA
• non-coding RNA

• Actins/metabolism
• Bacterial Proteins/metabolism
• Bacterial Toxins/metabolism
• Cell Membrane/metabolism
• Cell Membrane/microbiology
• Clathrin/metabolism
• Cytotoxins/metabolism
• Dynamins/metabolism
• HeLa Cells
• Heat-Shock Proteins/metabolism
• Hemolysin Proteins/metabolism
• Hep G2 Cells
• Hepatocytes/microbiology
• Host-Pathogen Interactions
• Humans
• Listeria monocytogenes/pathogenicity
• Listeria monocytogenes/physiology
• Microspheres
• Polystyrenes
• Pore Forming Cytotoxic Proteins/metabolism
• Protein-Tyrosine Kinases/metabolism

• P41 RR017573 NCRR NIH HHS
• GM52468 NIGMS NIH HHS
• R01 GM052468 NIGMS NIH HHS
• R37 GM052468 NIGMS NIH HHS
• R01 AI037657 NIAID NIH HHS
• RR017573 NCRR NIH HHS

Listeria monocytogenes targets accessible E-cadherin expressed on mucus-producing goblet cells to invade the intestinal tissue.

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.

Listeria monocytogenes is an opportunistic foodborne pathogen causing listeriosis, an often fatal infection leading to meningitis, sepsis, or infection of the fetus and abortion in susceptible individuals. It was recently found that the bacterium can also cause acute, self-limiting febrile gastroenteritis in healthy individuals. In the intestinal tract, L. monocytogenes penetrates the mucosa directly via enterocytes, or indirectly via invasion of Peyer's patches. Animal models for L. monocytogenes infection have provided many insights into the mechanisms of pathogenesis, and the development of new model systems has allowed the investigation of factors that influence adaptation to the gastrointestinal environment as well as adhesion to and invasion of the intestinal mucosa. The mucosal surfaces of the gastrointestinal tract are permanently exposed to an enormous antigenic load derived from the gastrointestinal microbiota present in the human bowel. The integrity of the important epithelial barrier is maintained by the mucosal immune system and its interaction with the commensal flora via pattern recognition receptors (PRRs). Here, we discuss recent advances in our understanding of the interaction of L. monocytogenes with the host immune system that triggers the antibacterial immune responses on the mucosal surfaces of the human gastrointestinal tract.

• dose-response
• uncertainty factors
• homeostatic mechanisms
• thresholds
• listeria monocytogenes

• Disease Outbreaks
• Female
• Food Microbiology
• Homeostasis
• Humans
• Listeria monocytogenes
• Listeriosis/prevention & control
• Pregnancy
• Pregnancy Complications, Infectious
• Public Health

• Adaptation, Physiological
• Animals
• Gastrointestinal Tract/microbiology
• Gene Expression Profiling
• Genome, Bacterial
• Host-Pathogen Interactions
• Humans
• Listeria monocytogenes/pathogenicity
• Listeria monocytogenes/physiology
• Listeriosis/metabolism
• Listeriosis/microbiology
• Virulence