Campylobacter Jejuni Infection Research Articles

A Systematic Review of Campylobacter jejuni Vaccine Candidates for Chickens.

Campylobacter jejuni infection linked to the consumption of contaminated poultry products is one of the leading causes of human enteric illness worldwide. Vaccination of chickens is one of the potential strategies that could be used to control C. jejuni colonization. To date, various C. jejuni vaccines using potential antigens have been evaluated, but a challenge in identifying the most effective formulation is the wide variability in vaccine efficacies reported. A systematic review was undertaken to compare C. jejuni vaccine studies. Based upon specific selection criteria eligible papers were identified and included in the analysis. Vaccine efficacy reported from different C. jejuni antigens, vaccine types, and vaccination regimens reported in these papers were reviewed. Our analysis shows that total outer membrane proteins and cysteine ABC transporter substrate-binding protein were among the most efficacious vaccine antigen candidates reported. This review also highlights the importance of the need for increased consistency in the way C. jejuni vaccine studies in poultry are designed and reported in order to be able to undertake a robust comparison of C. jejuni vaccine candidates.

The Probiotic Lactobacillus fermentum Biocenol CCM 7514 Moderates Campylobacter jejuni-Induced Body Weight Impairment by Improving Gut Morphometry and Regulating Cecal Cytokine Abundance in Broiler Chickens.

Simple SummaryHigh consumption of chicken meat and derived products has been associated with Campylobacter jejuni infections in humans. Probiotics have been exploited successfully with the aim of preventing colonization by unwanted microorganisms in birds. In this research, we investigated the effects of Lactobacillus fermentum Biocenol CCM 7514 supplementation on body weight, morphometry of the intestine and the cecal cytokine response. Probiotic-treated chickens showed higher body weight values than those exposed to C. jejuni or reared under control conditions. These differences in body weight were correlated to the overall characteristics of the small intestine, with larger villi and deeper crypts, observed in chickens administered with L. fermentum; such conditions are known to favor nutrient absorption. Likewise, body weight proved to be correlated to transcript abundance of IL-1β and IL-13. In probiotic-treated birds, such factors were upregulated in comparison to what was detected in C. jejuni-infected chickens; these interleukins are considered crucial in the response to invading pathogens. Clearly, these results show that administration of this probiotic strain lessens the negative effects elicited by C. jejuni and ultimately improves chicken body weight.This research was conducted to investigate if the administration of the probiotic Lactobacillus fermentum could influence body weight, intestinal morphometry and the cecal cytokine response in Campylobacter jejuni-infected chickens. Seventy-two 1-day old COBB 500 male chicks were allocated randomly into four experimental groups. (I) Control group (C), in which chicks were left untreated. (II) LB group, treated with L. fermentum. (III) Cj group, infected with C. jejuni and (IV) coexposure group in which both bacteria were administered. Body weight was registered and then all birds were slaughtered; samples from the small intestine and caecum were collected at 4- and 7-days post infection. The experiment lasted eleven days. Villi height and crypt depth ratios of the duodenum, jejunum and ileum were evaluated using appropriate software, while reverse transcription quantitative PCR (RT-qPCR) was utilized for assessing transcript levels of key cecal inflammatory cytokines (IL-1β, IL-18, IL-17, IL-15, IL13 and IL-4). Campylobacter-infected birds showed lower body weight values than those supplemented with the probiotic; these birds, in turn, proved to be heavier than those reared under control conditions. L. fermentum administration improved morphometrical parameters of the duodenum, jejunum and ileum; in general, villi were larger and crypts deeper than those identified in control conditions. Moreover, the negative effects elicited by C. jejuni were not observed in chickens exposed to the probiotic. Significant differences were also determined with regards to transcript abundance of all evaluated cytokines in the caecum. C. jejuni induced a downregulation of the studied interleukins; however, such a response was heightened by administration of L. fermentum, with an increase rate of transcription that promoted a more effective response to a C. jejuni infection. The effects of experimental treatments proved to vary between sampling points. Conclusively, these results demonstrate that L. fermentum lessens the negative effects elicited by C. jejuni on body weight by alleviating the impact on intestinal morphometry and cecal cytokine response, which ultimately improve chicken growth performance.

Murine Models for the Investigation of Colonization Resistance and Innate Immune Responses in Campylobacter Jejuni Infections.

Human infections with the food-borne pathogen Campylobacter jejuni are progressively increasing worldwide and constitute a significant socioeconomic burden to mankind. Intestinal campylobacteriosis in humans is characterized by bloody diarrhea, fever, abdominal pain, and severe malaise. Some individuals develop chronic post-infectious sequelae including neurological and autoimmune diseases such as reactive arthritis and Guillain-Barré syndrome. Studies unraveling the molecular mechanisms underlying campylobacteriosis and post-infectious sequelae have been hampered by the scarcity of appropriate experimental in vivo models. Particularly, conventional laboratory mice are protected from C. jejuni infection due to the physiological colonization resistance exerted by the murine gut microbiota composition. Additionally, as compared to humans, mice are up to 10,000 times more resistant to C. jejuni lipooligosaccharide (LOS) constituting a major pathogenicity factor responsible for the immunopathological host responses during campylobacteriosis. In this chapter, we summarize the recent progress that has been made in overcoming these fundamental obstacles in Campylobacter research in mice. Modification of the murine host-specific gut microbiota composition and sensitization of the mice to C. jejuni LOS by deletion of genes encoding interleukin-10 or a single IL-1 receptor-related molecule as well as by dietary zinc depletion have yielded reliable murine infection models resembling key features of human campylobacteriosis. These substantial improvements pave the way for a better understanding of the molecular mechanisms underlying pathogen-host interactions. The ongoing validation and standardization of these novel murine infection models will provide the basis for the development of innovative treatment and prevention strategies to combat human campylobacteriosis and collateral damages of C. jejuni infections.

Chemoenzymatic Synthesis of Campylobacter jejuni Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities.

Guillain-Barré syndrome is often caused by Campylobacter jejuni infection that has induced antibodies to the lipo-oligosaccharide (LOS) that cross-react with gangliosides at peripheral nerves causing polyneuropathy. To examine fine specificities of anti-ganglioside antibodies and develop a more robust platform for diagnosis and disease monitoring, we developed a chemoenzymatic approach that provided an unprecedented panel of oligosaccharides composed of the inner-core of the LOS of C. jejuni extended by various ganglioside mimics. The compounds and corresponding ganglio-oligosaccharides were printed as a microarray to examine binding specificities of lectins, anti-ganglioside antibodies, and serum antibodies of GBS patients. Although lectins and anti-ganglioside antibodies did not differentiate the ganglio-oligosaccharides and mimics, the patient serum samples bound much more strongly to the ganglioside mimics. The data indicate that antibodies have been elicited to a foreign epitope that includes a heptosyl residue unique of bacterial LOS and that these antibodies subsequently cross-react with lower affinity to gangliosides. The microarray detected anti-GM1a antibodies with high sensitivity and will be attractive for diagnosis, disease monitoring, and immunological research.

Whole-Genome Sequencing and Bioinformatic Analysis of Environmental, Agricultural, and Human Campylobacter jejuni Isolates From East Tennessee.

As a leading cause of bacterial-derived gastroenteritis worldwide, Campylobacter jejuni has a significant impact on human health in both the developed and developing worlds. Despite its prevalence as a human pathogen, the source of these infections remains poorly understood due to the mutation frequency of the organism and past limitations of whole genome analysis. Recent advances in both whole genome sequencing and computational methods have allowed for the high-resolution analysis of intraspecies diversity, leading multiple groups to postulate that these approaches may be used to identify the sources of Campylobacter jejuni infection. To address this hypothesis, our group conducted a regionally and temporally restricted sampling of agricultural and environmental Campylobacter sources and compared isolated C. jejuni genomes to those that caused human infections in the same region during the same time period. Through a network analysis comparing genomes from various sources, we found that human C. jejuni isolates clustered with those isolated from cattle and chickens, indicating these as potential sources of human infection in the region.

Laboratory investigation for one gastroenteritis outbreak caused by Campylobacter jejuni

Objective: To understand the etiological characteristics of an acute gastroenteritis outbreak. Methods: Real-time polymerase chain reaction (PCR) and bacteria cultures were performed for the samples, including stool samples from patients and cooks, environmental swabs, raw food material (chicken meat), collected during the outbreak. Pulsed-field gel electrophoresis, antibiotics susceptibility test and whole-genome sequencing were performed for the Campylobacter jejuni isolates. Results: Four stool samples from patients were positive for Campylobacter jejuni by real-time PCR, in which 1 Campylobacter jejuni strain was isolated from a case who had no antibiotic treatment. Twelve Campylobacter jejuni and 7 Campylobacter coli isolates were obtained from 4 raw chicken meat samples. The Campylobacter jejuni strain isolated from the case was resistant to nalidixic acid, ciprofloxacin, chloramphenicol, florfenicol and tetracycline. The MLST analysis with the whole-genome sequences confirmed that the Campylobacter jejuni isolate from the case belonged to ST10075. Antimicrobial resistance genes cmeABCR, tetO/M and blaOXA-61 were found in the genome of the isolate from the patient by the whole-genome sequencing. No mutation in 23S rRNA was found and the C257T mutation in gyrA was identified in this isolate. Conclusion: Laboratory analysis indicated that Campylobacter jejuni infection might be the major cause of this gastroenteritis outbreak.

S2864 A Rare Presentation of Immunoproliferative Small Intestinal Disease

INTRODUCTION: Immunoproliferative small intestinal disease (IPSID), is a form of extra-nodal marginal zone B-cell lymphoma, seen in young adults in the Mediterranean basin and Southeast Asia. It characterized by the production of monoclonal heavy chain without light chains that are deposited in the lamina propria, culminating in blunting of intestinal villi, malabsorption, and protein-losing enteropathy. It manifests as colicky abdominal pain, persistent diarrhea, malabsorption, weight loss and failure to thrive. IPSID is associated with chronic Campylobacter jejuni infection and has a range of presentation from lymphoid infiltration to malignant diffuse large-B-cell lymphoma, early stages of which are completely responsive to antibiotics. CASE DESCRIPTION/METHODS: A 50-year-old woman presented after syncope and a two-week history of persistent watery diarrhea and thirty-pound weight loss over six months (Table A). Four months prior, she was hospitalized in Nigeria for similar symptoms. She was ill-appearing and malnourished with a diffusely tender abdomen. Computed tomography revealed diffuse mesenteric lymphadenopathy. An extensive infectious (Table A) and non-infectious (Table B) was negative except for a positive Campylobacter stool antigen. Endoscopy revealed moderate gastritis and colitis, duodenal biopsy revealed blunted villi and lymphocytic infiltration (Figure A). Her diarrhea improved with antibiotics and she was discharged.One month after discharge, she presented with recurrence of symptoms. An extensive workup yielded the same results as before. Biopsy of mesenteric lymph nodes revealed reactive lymphadenitis. One year later, the patient presented to the hospital again, now with neck pain and dysphagia in addition to the prior GI symptoms. She was found to have cervical lymphadenopathy biopsy of which revealed lymphoma. She was diagnosed with IPSID Stage C initiated on chemotherapy. However, she succumbed to her disease. DISCUSSION: IPSID should be considered in all patients from endemic regions after other causes of infectious and non-infectious diarrhea and mesenteric lymphadenopathy are ruled out. Early diagnosis and treatment, at a stage responsive to antibiotics, may lead to resolution of the disease. In the case of our patient, Campylobacter stool antigen was persistently positive even after she had left an endemic region (West Africa) and received multiple courses of antibiotics, underscoring the puzzling nature of the source of her recurrent bacterial infection.Table 2.: Diarrhea and mesenteric lymphadenopathy can be caused by a multitude of pathology, which should be considered and ruled out because a diagnosis of IPSID is madeTable 1.: Initial presentation versus one month later versus one year laterFigure 1.: 4x magnification, Low power view of the small intestinal mucosa with marked villous blunting and expansion of lamina propria by small, mature lymphoid cells. Figure 2: 40x magnification, High power view of the small intestinal mucosa showing sheets of predominantly mature lymphoid cells with scattered plasma cells and eosinophils.

Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice.

Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

Epidemiological and Whole Genomic Sequencing Analysis of a Campylobacter jejuni Outbreak in Zhejiang Province, China, May 2019.

Campylobacter is well recognized as the leading cause of bacterial foodborne diarrheal disease worldwide with a very low outbreak reported in China. In May 2019, we investigated an outbreak of Campylobacter jejuni infections among students in a junior high school in Eastern China. Cases were interviewed to identify a common source of contamination. As cases were identified in the same school during a period of time, menus were reviewed and food items included in the questionnaire. Rectal swabs from school kitchen staff and suspected food items (raw chicken) from a local market from where the school food came were examined for C. jejuni. Pulsed-field gel electrophoresis and whole genome sequencing were performed to determine the relatedness of the isolates. To identify the source of the contamination, a case-control study was conducted. Forty-five cases were reported with diarrhea among 1696 students and staff. Stool samples for 10 of the 45 and 5 tested positive for C. jejuni. WGS analysis revealed a 0-4 single nucleotide variation in case-patient isolates. Although we were unable to identify the specific food item, a specific menu was identified as the potential source of the contamination (odds ratios = 20.82; 95% confidence interval = 6.472-66.957). In this menu, chicken was served. A food isolate collected from chicken in Zhejiang province in 2018 was positive for the same identical strain (5-7 single nucleotide polymorphisms). This is one of the few reports in China about outbreak caused by C. jejuni. This investigation illustrates the potential risk of outbreaks caused by Chinese cold dishes of chicken.

Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis

ABSTRACT Mechanisms of host–pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by C. jejuni, we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various Campylobacter species. A constructed deletion mutant ΔpepP of C. jejuni strain 81–176 grew as efficiently compared to isogenic wild-type (WT) or pepP complemented bacteria. To shed light on the potential role of this protease in mediating immunopathological responses in the mammalian host, we perorally challenged microbiota-depleted IL-10−/- mice with these strains. All strains stably colonized the murine gastrointestinal tract with comparably high loads. Remarkably, pepP deficiency was associated with less severe induced malaise, with less distinct apoptotic and innate immune cell responses, but also with more pronounced proliferative/regenerative epithelial cell responses in the large intestine at d6post-infection. Furthermore, pro-inflammatory mediators were lower in the colon, ileum, and mesenteric lymph nodes of mice that had been challenged with the ΔpepP mutant compared to the WT or pepP complemented strains. This also held true for extra-intestinal organs including liver, kidneys, and lungs, and, strikingly, to systemic compartments. Taken together, protease PepP is a novel virulence determinant involved in mediating campylobacteriosis. The finding that apoptosis in the colon is significantly diminished in mice infected with the pepP mutant highlights the epithelial layer as the first and main target of PepP in the intestine.

Fc-gamma IIIa-V158F receptor polymorphism contributes to the severity of Guillain-Barré syndrome.

ObjectiveGuillain‐Barré syndrome (GBS) is a rare, life‐threatening disorder of the peripheral nervous system. Immunoglobulin G Fc‐gamma receptors (FcγRs) mediate and regulate diverse effector functions and are involved in the pathogenesis of GBS. We investigated whether the FcγR polymorphisms FcγRIIa H/R131 (rs1801274), FcγRIIIa V/F158 (rs396991), and FcγRIIIb NA1/NA2, and their haplotype patterns affect the affinity of IgG‐FcγR interactivity and influence GBS susceptibility and severity.MethodsWe determined FcγR polymorphisms in 303 patients with GBS and 302 ethnically matched healthy individuals from Bangladesh by allele‐specific polymerase chain reaction. Pairwise linkage disequilibrium and haplotype patterns were analyzed based on D ´statistics and the genotype package of R statistics, respectively. Logistic regression analysis and Fisher’s exact test with corrected P (Pc) values were employed for statistical comparisons.ResultsFcγRIIIa‐V158F was associated with the severe form of GBS compared to the mild form (P = 0.005, OR = 2.24, 95% CI = 1.28–3.91; Pc = 0.015); however, FcγR genotypes and haplotype patterns did not show any association with GBS susceptibility compared to healthy controls. FcγRIIIa‐V/V158 and FcγRIIIb‐NA2/2 were associated with recent Campylobacter jejuni infection (P ≤ 0.001, OR = 0.36, 95% CI = 0.23–0.56; Pc ≤ 0.003 and P = 0.004, OR = 1.70, 95% CI = 1.18–2.44; Pc ≤ 0.012, respectively). Haplotype 1 (FcγRIIa‐H131R‐ FcγRIIIa‐V158F‐ FcγRIIIb‐NA1/2) and the FcγRIIIb‐NA2/2 genotype were more prevalent among anti‐GM1 antibody‐positive patients (P = 0.031, OR = 9.61, 95% CI = 1.24–74.77, Pc = 0.279; P = 0.027, OR = 1.62, 95% CI = 1.06–2.5, Pc = 0.081, respectively).InterpretationFcγR polymorphisms and haplotypes are not associated with susceptibility to GBS, though the FcγRIIIa‐V158F genotype is associated with the severity of GBS.

Campylobacter jejuni infection associated with miscarriage, a case report and literature review

Campylobacter jejuni is recognized as a cause of miscarriage in animals, but rarely in humans. We describe here a case of spontaneous miscarriage at 12 weeks of gestation associated with Campylobacter jejuni bacteremia following digestive disorders. The patient was treated with azithromycin with good clinical evolution and underwent uterine aspiration during hospitalization. In our review of the literature, we found only 12 other miscarriages due to C. jejuni infections. Clinicians should consider this cause of miscarriage in febrile pregnant women, as the bacterium is resistant to many beta-lactam antibiotics, and macrolides are the first-line treatment.

Immunization with cytolethal distending toxin B produces autoantibodies to vinculin and small bowel bacterial changes in a rat model of postinfectious irritable bowel syndrome.

Recent data substantiate the importance of acute gastroenteritis in the development of irritable bowel syndrome (IBS). An animal model of postinfectious IBS determined the importance of cytolethal distending toxin B (CdtB) during live Campylobacter jejuni infection and its development of autoimmunity to vinculin. In this study, we examine whether subcutaneous exposure to CdtB alone is sufficient to produce the postinfectious IBS effect and autoimmunity. Sixty adult Sprague Dawley rats were randomized into 2 groups to receive subcutaneous injection of either CdtB or vehicle and administered a booster injection of the same product 3weeks later. Serum was collected for anti-CdtB and anti-vinculin titers. Duodenal and ileal luminal contents for total eubacterial qPCR, and ileal bowel segments were harvested for vinculin and ileal expression. In a second experiment, 4 adult, Sprague Dawley rats were injected with either Cy7-labeled anti-CdtB and anti-vinculin antibodies were injected into the tail vein and imaged to determine organ localization of the antibodies. Rats that received CdtB increased in serum anti-CdtB after injection. CdtB exposure also precipitated significant elevation in anti-vinculin antibodies (P<.001). This was associated with a reduction in intestinal vinculin expression (P<.001) that negatively correlated with serum anti-CdtB levels. CdtB exposure was also associated with greater levels of duodenal (P<.001) and ileal (P<.01) bacteria by qPCR that positively correlated with anti-CdtB levels. Rats injected with CdtB developed a postinfectious IBS-like phenotype and autoimmunity to vinculin with corresponding reduction in intestinal vinculin expression.

The conundrum of colonization resistance against Campylobacter reloaded: The gut microbota composition in conventional mice does not prevent from Campylobacter coli infection.

The physiological colonization resistance exerted by the murine gut microbiota prevents conventional mice from Campylobacter jejuni infection. In the present study we addressed whether this also held true for Campylobacter coli. Following peroral application, C. coli as opposed to C. jejuni could stably establish within the gastrointestinal tract of conventionally colonized mice until 3 weeks post-challenge. Neither before nor after either Campylobacter application any changes in the gut microbiota composition could be observed. C. coli, but not C. jejuni challenge was associated with pronounced regenerative, but not apoptotic responses in colonic epithelia. At day 21 following C. coli versus C. jejuni application mice exhibited higher numbers of adaptive immune cells including T-lymphocytes and regulatory T-cells in the colonic mucosa and lamina propria that were accompanied by higher large intestinal interferon-γ (IFN-γ) concentrations in the former versus the latter but comparable to naive levels. Campylobacter application resulted in decreased splenic IFN-γ, tumor necrosis factor-α (TNF-α), and IL-6 concentrations, whereas IL-12p70 secretion was increased in the spleens at day 21 following C. coli application only. In either Campylobacter cohort decreased IL-10 concentrations could be measured in splenic and serum samples. In conclusion, the commensal gut microbiota prevents mice from C. jejuni, but not C. coli infection.

Virulence Traits of Inpatient Campylobacter jejuni Isolates, and a Transcriptomic Approach to Identify Potential Genes Maintaining Intracellular Survival.

There are still major gaps in our understanding of the bacterial factors that influence the outcomes of human Campylobacter jejuni infection. The aim of this study was to compare the virulence-associated features of 192 human C. jejuni strains isolated from hospitalized patients with diarrhoea (150/192, 78.1%), bloody diarrhoea (23/192, 11.9%), gastroenteritis (3/192, 1.6%), ulcerative colitis (3/192, 1.5%), and stomach ache (2/192, 1.0%). Traits were analysed with genotypic and phenotypic methods, including PCR and extracellular matrix protein (ECMP) binding, adhesion, and invasion capacities. Results were studied alongside patient symptoms, but no distinct links with them could be determined. Since the capacity of C. jejuni to invade host epithelial cells is one of its most enigmatic attributes, a high throughput transcriptomic analysis was performed in the third hour of internalization with a C. jejuni strain originally isolated from bloody diarrhoea. Characteristic groups of genes were significantly upregulated, outlining a survival strategy of internalized C. jejuni comprising genes related (1) to oxidative stress; (2) to a protective sheath formed by the capsule, LOS, N-, and O- glycosylation systems; (3) to dynamic metabolic activity supported by different translocases and the membrane-integrated component of the flagellar apparatus; and (4) to hitherto unknown genes.

Novel Clinical Campylobacter jejuni Infection Models Based on Sensitization of Mice to Lipooligosaccharide, a Major Bacterial Factor Triggering Innate Immune Responses in Human Campylobacteriosis.

Human Campylobacter jejuni infections inducing campylobacteriosis including post-infectious sequelae such as Guillain-Barré syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.

Anthropogenic landscapes increase Campylobacter jejuni infections in urbanizing banded mongoose (Mungos mungo): A one health approach.

BackgroundCampylobacter is a common, but neglected foodborne-zoonotic pathogen, identified as a growing cause of foodborne disease worldwide. Wildlife and domestic animals are considered important reservoirs, but little is known about pathogen infection dynamics in free-ranging mammalian wildlife particularly in sub-Saharan Africa. In countries like Botswana, there is significant overlap between humans and wildlife, with the human population having one of the highest HIV infection rates in the world, increasing vulnerability to infection.Methodology/Principal findingsWe investigated Campylobacter occurrence in archived human fecal samples (children and adults, n = 122, 2011), feces from free-ranging banded mongooses (Mungos mungo, n = 201), surface water (n = 70), and river sediment samples (n = 81) collected in 2017 from the Chobe District, northern Botswana. Campylobacter spp. was widespread in humans (23.0%, 95% CI 13.9–35.4%), with infections dominantly associated with C. jejuni (82.1%, n = 28, 95% CI 55.1–94.5%). A small number of patients presented with asymptomatic infections (n = 6). While Campylobacter spp. was rare or absent in environmental samples, over half of sampled mongooses tested positive (56%, 95% CI 45.6–65.4%). Across the urban-wilderness continuum, we found significant differences in Campylobacter spp. detection associated with the type of den used by study mongooses. Mongooses utilizing man-made structures as den sites had significantly higher levels of C. jejuni infection (p = 0.019) than mongooses using natural dens. Conversely, mongooses using natural dens had overall higher levels of detection of Campylobacter at the genus level (p = 0.001).ConclusionsThese results suggest that landscape features may have important influences on Campylobacter species exposure and transmission dynamics in wildlife. In particular, data suggest that human-modified landscapes may increase C. jejuni infection, a primarily human pathogen, in banded mongooses. Pathogen circulation and transmission in urbanizing wildlife reservoirs may increase human vulnerability to infection, findings that may have critical implications for both public and animal health in regions where people live in close proximity to wildlife.

Contribution of Epithelial Apoptosis and Subepithelial Immune Responses in Campylobacter jejuni-Induced Barrier Disruption.

Campylobacter jejuni is a widespread zoonotic pathogen and the leading bacterial cause of foodborne gastroenteritis in humans. Previous infection studies showed disruption of intercellular contacts, induction of epithelial apoptosis, and immune activation, all three contributing to intestinal barrier dysfunction leading to diarrhea. The present study aims to determine the impact of subepithelial immune cells on intestinal barrier dysfunction during Campylobacter jejuni infection and the underlying pathological mechanisms. Infection was performed in a co-culture of confluent monolayers of the human colon cell line HT-29/B6-GR/MR and THP-1 immune cells. Twenty-two hours after infection, transepithelial electrical resistance (TER) was decreased by 58 ± 6% compared to controls. The infection resulted in an increase in permeability for fluorescein (332 Da; 4.5-fold) and for FITC-dextran (4 kDa; 3.5-fold), respectively. In contrast, incubation of the co-culture with the pan-caspase inhibitor Q-VD-OPh during the infection resulted in a complete recovery of the decrease in TER and a normalization of flux values. Fluorescence microscopy showed apoptotic fragmentation in infected cell monolayers resulting in a 5-fold increase of the apoptotic ratio, accompanied by an increased caspase-3 cleavage and caspase-3/7 activity, which both were not present after Q-VD-OPh treatment. Western blot analysis revealed increased claudin-1 and claudin-2 protein expression. Inhibition of apoptosis induction did not normalize these tight junction changes. TNFα concentration was increased during the infection in the co-culture. In conclusion, Campylobacter jejuni infection and the consequent subepithelial immune activation cause intestinal barrier dysfunction mainly through caspase-3-dependent epithelial apoptosis. Concomitant tight junction changes were caspase-independent. Anti-apoptotic and immune-modulatory substances appear to be promising agents for treatment of campylobacteriosis.

MLST-based genetic relatedness of Campylobacter jejuni isolated from chickens and humans in Poland.

Campylobacter jejuni infection is one of the most frequently reported foodborne bacterial diseases worldwide. The main transmission route of these microorganisms to humans is consumption of contaminated food, especially of chicken origin. The aim of this study was to analyze the genetic relatedness of C. jejuni from chicken sources (feces, carcasses, and meat) and from humans with diarrhea as well as to subtype the isolates to gain better insight into their population structure present in Poland. C. jejuni were genotyped using multilocus sequence typing (MLST) and sequence types (STs) were assigned in the MLST database. Among 602 isolates tested, a total of 121 different STs, including 70 (57.9%) unique to the isolates' origin, and 32 STs that were not present in the MLST database were identified. The most prevalent STs were ST464 and ST257, with 58 (9.6%) and 52 (8.6%) C. jejuni isolates, respectively. Isolates with some STs (464, 6411, 257, 50) were shown to be common in chickens, whereas others (e.g. ST21 and ST572) were more often identified among human C. jejuni. It was shown that of 47 human sequence types, 26 STs (106 isolates), 23 STs (102 isolates), and 29 STs (100 isolates) were also identified in chicken feces, meat, and carcasses, respectively. These results, together with the high and similar proportional similarity indexes (PSI) calculated for C. jejuni isolated from patients and chickens, may suggest that human campylobacteriosis was associated with contaminated chicken meat or meat products or other kinds of food cross-contaminated with campylobacters of chicken origin. The frequency of various sequence types identified in the present study generally reflects of the prevalence of STs in other countries which may suggest that C. jejuni with some STs have a global distribution, while other genotypes may be more restricted to certain countries.

Gastroenteritis Outbreak Caused by Campylobacter jejuni - Beijing, China, August, 2019.

What is already known about this topic? Campylobacter genus bacteria are recognized as some of the leading causes of the bacterial diarrheal illness in both developing and developed countries. Recent pilot surveillance study revealed Campylobacter is the most common pathogen in the diarrheal cases using the enhanced filtration methods in Beijing. One outbreak caused by multi-drug resistant Campylobacter coli ( C. coli ) was identified in 2018. What is added by this report? This is the first identified gastroenteritis outbreak caused by local Campylobacter jejuni (C. jejuni) infection in Beijing. A total of 14 patients were identified from August 23 to 26, 2019. The epidemiological investigation indicated that all of the patients worked at the same factory and the diarrhea happened after the same meal supplied from one company which service the meal delivery. Fourteen C. jejuni isolates were obtained from 12 patients and 2 food workers. Whole Genome Sequencing (WGS) analysis indicated this outbreak was caused by one highly clonal C. jejuni. What are the implications for public health practice? Campylobacter is the major foodborne pathogen in the world. Surveillance and risk assessment for Campylobacter infection particularly for Guillain-Barré Syndrome (GBS) associated C. jejuni infection in China should closely monitored.