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Helicobacter spp., including the well-known human gastric pathogen H. pylori, can cause gastric diseases in humans and other mammals. They are Gram-negative bacteria that colonize the gastric epithelium and use their multiple flagella to move across the protective gastric mucus layer. The flagella of different Helicobacter spp. vary in their location and number. This review focuses on the swimming characteristics of different species with different flagellar architectures and cell shapes. All Helicobacter spp. use a run-reverse-reorient mechanism to swim in aqueous solutions, as well as in gastric mucin. Comparisons of different strains and mutants of H. pylori varying in cell shape and the number of flagella show that their swimming speed increases with an increasing number of flagella and is somewhat enhanced with a helical cell body shape. The swimming mechanism of H. suis, which has bipolar flagella, is more complex than that of unipolar H. pylori. H. suis exhibits multiple modes of flagellar orientation while swimming. The pH-dependent viscosity and gelation of gastric mucin significantly impact the motility of Helicobacter spp. In the absence of urea, these bacteria do not swim in mucin gel at pH < 4, even though their flagellar bundle rotates.

Background The gut microbiome is altered in patients with inflammatory bowel disease, yet how these alterations contribute to intestinal inflammation is poorly understood. Murine models have demonstrated the importance of the microbiome in colitis since colitis fails to develop in many genetically susceptible animal models when re-derived into germ-free environments. We have previously shown that Wiskott-Aldrich syndrome protein (WASP)-deficient mice (Was−/−) develop spontaneous colitis, similar to human patients with loss-of-function mutations in WAS. Furthermore, we showed that the development of colitis in Was−/− mice is Helicobacter dependent. Here, we utilized a reductionist model coupled with multi-omics approaches to study the role of host-microbe interactions in intestinal inflammation. Results Was−/− mice colonized with both altered Schaedler flora (ASF) and Helicobacter developed colitis, while those colonized with either ASF or Helicobacter alone did not. In Was−/− mice, Helicobacter relative abundance was positively correlated with fecal lipocalin-2 (LCN2), a marker of intestinal inflammation. In contrast, WT mice colonized with ASF and Helicobacter were free of inflammation and strikingly, Helicobacter relative abundance was negatively correlated with LCN2. In Was−/− colons, bacteria breach the mucus layer, and the mucosal relative abundance of ASF457 Mucispirillum schaedleri was positively correlated with fecal LCN2. Meta-transcriptomic analyses revealed that ASF457 had higher expression of genes predicted to enhance fitness and immunogenicity in Was−/− compared to WT mice. In contrast, ASF519 Parabacteroides goldsteinii’s relative abundance was negatively correlated with LCN2 in Was−/− mice, and transcriptional analyses showed lower expression of genes predicted to facilitate stress adaptation by ASF519 in Was−/−compared to WT mice. Conclusions These studies indicate that the effect of a microbe on the immune system can be context dependent

© 2020, Society for Mucosal Immunology. Mice deficient in the IL-10 pathway are the most widely used models of intestinal immunopathology. IL-17A is strongly implicated in gut disease in mice and humans, but conflicting evidence has drawn IL-17’s role in the gut into question. IL-22 regulates antimicrobial and repair activities of intestinal epithelial cells (IECs) and is closely associated with IL-17A responses but it’s role in chronic disease is uncertain. We report that IL-22, like IL-17A, is aberrantly expressed in colitic Il10−/− mice. While IL-22+Th17 cells were elevated in the colon, IL-22-producing ILC3s were highly enriched in the small intestines of Il10−/− mice. Remarkably, Il10−/−Il22−/− mice did not develop colitis despite retaining high levels of Th17 cells and remaining colonized with colitogenic Helicobacter spp. Accordant with IL-22-induced IEC proliferation, the epithelia hyperplasia observed in Il10−/− animals was reversed in Il10−/−Il22−/− mice. Also, the high levels of antimicrobial IL-22-target genes, including Reg3g, were normalized in Il10−/−Il22−/− mice. Consistent with a heightened antimicrobial environment, Il10−/− mice had reduced diversity of the fecal microbiome that was reestablished in Il10−/−Il22−/− animals. These data suggest that spontaneous colitis in Il10−/− mice is driven by IL-22 and implicates an underappreciated IL-10/IL-22 axis in regulating intestinal homeostasis.

© Copyright © 2020 Batac, Miller, Moriarty, Shen, Fox and Ottemann. Southern sea otters (Enhydra lutris nereis) are threatened marine mustelids that commonly have gastric ulcers with secondary hemorrhage (melena) as a contributing cause of death. Although Helicobacter spp. infections are known to cause gastric ulcers and gastritis in humans and ferrets, it is unknown if the sea otter bacterium, H. enhydrae sp. nov., causes similar gastric pathology. Determining whether Helicobacter detection is associated with sea otter gastric pathology is the first step toward using this information to expedite diagnosis and treatment. We investigated the proportion of Helicobacter infections in 46 necropsied southern sea otters via quantitative real-time polymerase chain reaction (qPCR) of the 16S rRNA gene. Helicobacter DNA was detected in fresh-frozen and formalin-fixed gastric body and pyloric tissues using Helicobacter genus-specific 16S rRNA primers. Data from gross necropsy and histopathology were analyzed for associations between Helicobacter detection via qPCR and presence/absence of gastric pathology. ETEST® gradient strips were utilized to investigate antimicrobial minimum inhibitory concentrations for H. enhydrae isolates. Helicobacter spp. were detected in the gastric tissue of 85% of sea otters in this study. Fresh-frozen samples were more commonly Helicobacter qPCR-positive than formalin-fixed tissue, indicating variable sensitivity of detection in relation to post-necropsy tissue processing methods. Diagnosis of gastric ulcers at necropsy was significantly associated with Helicobacter qPCR detection in gastric mucosa (P = 0.005), while age, sex, presence of melena, shark trauma, and protozoal infection were not associated (P > 0.1). Helicobacter enhydrae isolates were sensitive to clarithromycin and tetracycline in vitro at physiologically relevant concentrations. Overall, this work suggests that Helicobacter spp. might be commonly found in southern sea otters, par

© Copyright © 2020 Batac, Miller, Moriarty, Shen, Fox and Ottemann. Southern sea otters (Enhydra lutris nereis) are threatened marine mustelids that commonly have gastric ulcers with secondary hemorrhage (melena) as a contributing cause of death. Although Helicobacter spp. infections are known to cause gastric ulcers and gastritis in humans and ferrets, it is unknown if the sea otter bacterium, H. enhydrae sp. nov., causes similar gastric pathology. Determining whether Helicobacter detection is associated with sea otter gastric pathology is the first step toward using this information to expedite diagnosis and treatment. We investigated the proportion of Helicobacter infections in 46 necropsied southern sea otters via quantitative real-time polymerase chain reaction (qPCR) of the 16S rRNA gene. Helicobacter DNA was detected in fresh-frozen and formalin-fixed gastric body and pyloric tissues using Helicobacter genus-specific 16S rRNA primers. Data from gross necropsy and histopathology were analyzed for associations between Helicobacter detection via qPCR and presence/absence of gastric pathology. ETEST® gradient strips were utilized to investigate antimicrobial minimum inhibitory concentrations for H. enhydrae isolates. Helicobacter spp. were detected in the gastric tissue of 85% of sea otters in this study. Fresh-frozen samples were more commonly Helicobacter qPCR-positive than formalin-fixed tissue, indicating variable sensitivity of detection in relation to post-necropsy tissue processing methods. Diagnosis of gastric ulcers at necropsy was significantly associated with Helicobacter qPCR detection in gastric mucosa (P = 0.005), while age, sex, presence of melena, shark trauma, and protozoal infection were not associated (P > 0.1). Helicobacter enhydrae isolates were sensitive to clarithromycin and tetracycline in vitro at physiologically relevant concentrations. Overall, this work suggests that Helicobacter spp. might be commonly found in southern sea otters, par

© 2020, Society for Mucosal Immunology. Mice deficient in the IL-10 pathway are the most widely used models of intestinal immunopathology. IL-17A is strongly implicated in gut disease in mice and humans, but conflicting evidence has drawn IL-17’s role in the gut into question. IL-22 regulates antimicrobial and repair activities of intestinal epithelial cells (IECs) and is closely associated with IL-17A responses but it’s role in chronic disease is uncertain. We report that IL-22, like IL-17A, is aberrantly expressed in colitic Il10−/− mice. While IL-22+Th17 cells were elevated in the colon, IL-22-producing ILC3s were highly enriched in the small intestines of Il10−/− mice. Remarkably, Il10−/−Il22−/− mice did not develop colitis despite retaining high levels of Th17 cells and remaining colonized with colitogenic Helicobacter spp. Accordant with IL-22-induced IEC proliferation, the epithelia hyperplasia observed in Il10−/− animals was reversed in Il10−/−Il22−/− mice. Also, the high levels of antimicrobial IL-22-target genes, including Reg3g, were normalized in Il10−/−Il22−/− mice. Consistent with a heightened antimicrobial environment, Il10−/− mice had reduced diversity of the fecal microbiome that was reestablished in Il10−/−Il22−/− animals. These data suggest that spontaneous colitis in Il10−/− mice is driven by IL-22 and implicates an underappreciated IL-10/IL-22 axis in regulating intestinal homeostasis.

Blue iguanas (Cyclura lewisi) are endangered reptiles found only on Grand Cayman. Previously, DNA for a novel Helicobacter species GCBI1 was detected in sick and dead iguanas. In the current study, fecal and cloacal swab samples were obtained from 25 iguanas. Through molecular and microbiological techniques, a novel Helicobacter species was cultured from feces and characterized, for whom we propose the name Helicobacter cyclurae. This novel helicobacter had a prevalence of 56% by PCR and 20% by culture in samples analyzed. The type strain MIT 16-1353 was catalase, oxidase, and gamma-glutamyl transpeptidase positive. By electron microscopy, H. cyclurae has a curved rod morphology and a single sheathed polar flagellum. Phylogenetic analysis using 16S rRNA, gyrB, and hsp60 indicated that these strains were most closely related to Helicobacter sp. 12502256-12 previously isolated from lizards. H. cyclurae has a 1.91-Mb genome with a GC content of 33.37%. There were 1,969 genes with four notable virulence genes: high temperature requirement-A protein-secreted serine protease, gamma-glutamyl transpeptidase, fibronectin/fibrinogen binding protein, and neutrophil-activating protein. Whole-genome phylogeny, average nucleotide identity, and digital DNA–DNA hybridization analysis confirmed that H. cyclurae is a novel species, and the first helicobacter cultured and characterized from blue iguanas.

Copyright: © 2021 Conley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The Blue Iguana Recovery Programme maintains a captive breeding and head-starting program for endangered Grand Cayman blue iguanas (Cyclura lewisi) on Grand Cayman, Cayman Islands. In May 2015, program staff encountered two lethargic wild Grand Cayman blue iguanas within the Queen Elizabeth II Botanic Park (QEIIBP). Spiral-shaped bacteria were identified on peripheral blood smears from both animals, which molecular diagnostics identified as a novel Helicobacter species (provisionary name Helicobacter sp. GCBI1). Between March 2015 and February 2017, 11 Grand Cayman blue iguanas were identified with the infection. Two of these were found dead and nine were treated; five of the nine treated animals survived the initial infection. Phylogenetic analysis of the 16S rRNA gene suggests Helicobacter sp. GCBI1 is most closely related to Helicobacter spp. in chelonians. We developed a Taqman qPCR assay specific for Helicobacter sp. GCBI1 to screen tissue and/or blood samples from clinical cases, fecal and cloacal samples from clinically healthy Grand Cayman blue iguanas, including previously infected and recovered iguanas, and iguanas housed adjacent to clinical cases. Fecal and/or cloacal swab samples were all negative, suggesting that Grand Cayman blue iguanas do not asymptomatically carry this organism nor shed this pathogen per cloaca post infection. Retrospective analysis of a 2014 mortality event affecting green iguanas (Iguana iguana) from a separate Grand Cayman location identified Helicobacter sp. GCBI1 in two of three cases. The source of infection and mode of transmission are yet to be confirmed. Analysis of rainfall data reveal that all infections occurred during a multi-year dry period, and most occu

Cotton-top tamarins (CTTs) are an ideal model of human inflammatory bowel disease (IBD) because these animals develop multigenerational, lower bowel cancer. We previously isolated and characterized a novel enterohepatic Helicobacter species, Helicobacter saguini, from CTTs with IBD and documented that H. saguini infection in germfree C57BL IL-10-/- mice recapitulates IBD, suggesting that H. saguini influences IBD etiopathogenesis. In this study, we utilized a germfree IL-10-/- model to illustrate that H. saguini infection can naturally transmit and infect four generations and cause significant intestinal inflammatory pathology. Additionally, whole-genome sequencing of representative H. saguini isolates from each generation of IL-10-/- mice revealed gene mutations suggestive of multigenerational evolution. Overall, these results support that specific bacterial species with pathogenic potential, like H. saguini, are transmissible microorganisms in the etiopathogenesis of IBD in CTTs and reinforces the importance of specific microbiota in the pathogenesis of IBD in humans.IMPORTANCE While family history is a significant risk factor for developing inflammatory bowel disease (IBD), it is unclear whether the microbiome from parents is a transmissible influence on disease in their offspring. Furthermore, it is unknown whether IBD-associated microbes undergo genomic adaptations during multigenerational transmission and chronic colonization in their hosts. Herein, we show that a single bacterial species, Helicobacter saguini, isolated from a nonhuman primate species with familial IBD, is transmissible from parent to offspring in germfree IL-10-/- mice and causes multigenerational IBD. Additionally, whole-genome sequence analysis of H. saguini isolated from different mouse generations identified microevolutions in environmental interaction, nutrient metabolism, and virulence factor genes that suggest that multigenerational transmission may promote adaptations related to colon, NIH (Grants T32-OD010978, P30-ES002109, P01-CA028848, and R35-CA210088)

Campylobacter species are being increasingly isolated and associated with disease in humans and animals. Here, we describe four draft genome sequences of Campylobacter species from nonhuman primates. These include Campylobacter troglodytis, isolated from wild chimpanzees, and two likely new Campylobacter species isolated from a lemur, common marmoset, and cotton-top tamarin., NIH (Grants T32-OD010978, P30-ES002109, R01-OD01141, and R01-CA067529)

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. A fast-growing Mycobacterium species was cultured from draining, purulent lesions on the caudal abdomen of a 12-year-old male domestic long-haired cat. Whole-genome sequencing identified the organism as Mycobacterium porcinum.

Background: Helicobacter canis has been associated with hepatobiliary and gastrointestinal disease in dogs, cats, and humans. Infection has not been documented in other species. Materials and Methods: Sheep feces subjected to microaerobic culture. Isolates were characterized by genus-specific PCR, restriction fragment length polymorphism, biochemical profiling, and 16S rRNA sequence analysis. Results: Helicobacter canis was isolated from sheep feces and confirmed by the above methods. These isolates are distinct from other sheep-origin enterohepatic Helicobacter species previously isolated. Conclusions: This study identifies sheep as H. canis reservoirs potentially important in zoonotic or foodborne transmission. ©2014, NIH (grant no. T32 RR007036), NIH (grant no. R01 OD011141), NIH (grant no. P01 CA028842), NIH (grant no. P30 ES02109)

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Background: The aim of this study was to longitudinally investigate the prevalence and characterization of Campylobacter spp. from non-human primates primate (NHP) with a history of endemic diarrhea housed at Como Park Zoo. Methods: Fecal samples from 33 symptom-free NHP belonging to eight different species were collected weekly for 9 weeks. Species-level characterization and phylogenetic analysis of isolates included biochemical testing and 16S rRNA sequencing. Results: Campylobacter spp. were isolated from the feces of 42% (14/33) of the primates. Three Campylobacter spp. (C upsaliensis, C jejuni, and novel Campylobacter sp.) were identified from three NHP species. A possible positive host Campylobacter species-specificity was observed. However, no statistical association was observed between the isolation of Campylobacter spp. and age and sex of the animal. Conclusions: The study revealed the value of conducting repeated fecal sampling to establish the overall prevalence of Campylobacter in zoo-maintained NHP; it also importantly identifies a novel Campylobacter sp. isolated from white-faced saki monkeys., NIH (grant no. P30-ES002109), NIH (grant no. R01-OD011141), NIH (grant no. T32-OD010978)

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (T[subscript reg]) cell responses. However, the bacteria that induce effector T (T[subscript eff]) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both T[subscript reg] cell responses during homeostasis and T[subscript eff] cell responses during colitis, as suggested by an increased overlap between the T[subscript eff]/T[subscript reg] TCR repertoires with colitis. Four of six T[subscript reg] TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion of luminal Bacteroides species seen during colitis did not trigger a commensurate T[subscript eff] cell response. Unlike other T[subscript reg] cell-inducing bacteria, Helicobacter species are known pathobionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent T[subscript reg] or T[subscript eff] cell responses to facilitate intestinal tolerance or inflammation. ©2017, NIH (grant no. P30ES 002109), NIH (grant no. T32OD10978-29)

Background: Helicobacter saguini is a novel enterohepatic Helicobacter species isolated from captive cotton top tamarins with chronic colitis and colon cancer. Monoassociated H. saguini infection in gnotobiotic IL-10 −/− mice causes typhlocolitis and dysplasia; however, the virulent mechanisms of this species are unknown. Gamma-glutamyltranspeptidase (GGT) is an enzymatic virulence factor expressed by pathogenic Helicobacter and Campylobacter species that inhibits host cellular proliferation and promotes inflammatory-mediated gastrointestinal pathology. The aim of this study was to determine if H. saguini expresses an enzymatically active GGT homologue with virulence properties. Experimental procedures: Two putative GGT paralogs (HSGGT1 and HSGGT2) identified in the H. saguini genome were bioinformatically analysed to predict enzymatic functionality and virulence potential. An isogenic knockout mutant strain and purified recombinant protein of HSGGT1 were created to study enzymatic activity and virulence properties by in vitro biochemical and cell culture experiments. Results: Bioinformatic analysis predicted that HSGGT1 has enzymatic functionality and is most similar to the virulent homologue expressed by Helicobacter bilis, whereas HSGGT2 contains putatively inactivating mutations. An isogenic knockout mutant strain and recombinant HSGGT1 protein were successfully created and demonstrated that H. saguini has GGT enzymatic activity. Recombinant HSGGT1 protein and sonicate from wild-type but not mutant H. saguini inhibited gastrointestinal epithelial and lymphocyte cell proliferation without evidence of cell death. The antiproliferative effect by H. saguini sonicate or recombinant HSGGT1 protein could be significantly prevented with glutamine supplementation or the GGT-selective inhibitor acivicin. Recombinant HSGGT1 protein also induced proinflammatory gene expression in colon epithelial cells. Conclusions: This study shows that H. saguini may express GGT as a pote, National Institutes of Health (U.S.) (Grant T32‐OD010978), National Institutes of Health (U.S.) (Grant P30‐ES002109), National Institutes of Health (U.S.) (Grant R01‐OD01141)

Background: Of all human cancers, gastric carcinoma is the one of the leading causes of death. Helicobacter pylori is considered a major etiologic agent of this disease. Spontaneously occurring gastric carcinoma is a rare diagnosis in nonhuman primates. A 2011 case report documented a high incidence of gastric adenocarcinoma in a closed colony of captive sooty mangabeys (Cercebus atys). However, H. pylori infection was not detected in these animals. Materials and Methods: In this study, using archived formalin-fixed, paraffin-embedded stomach sections of these animals alternative methodologies were used to identify H. pylori and other non-H. pylori Helicobacter species. In addition, two additional cases of sooty mangabeys with metastatic gastric carcinoma are characterized. Results: Using fluorescent in situ hybridization, we identified gastric H. suis in 75% of archived and new gastric carcinoma cases. In the two newly reported cases, H. suis and a novel Helicobacter species were detected via PCR and sequence analysis of the 16S rRNA gene. H. pylori was not identified in any of the gastric carcinoma cases via FISH and/or PCR and sequence analysis of Helicobacter spp. in DNA from of available tissues. Conclusions: This report is the first to characterize Helicobacter species infection in spontaneous gastric carcinoma with metastatic potential in nonhuman primates. ©2016, NIH (grant no. T32-OD010978), NIH (grant no. P30-ES002109), NIH (grant no. P01-CA028842), NIH (grant no. R01-CA0 93405)