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Li Zhang - One of the best experts on this subject based on the ideXlab platform.

  • analysis of complete Campylobacter Concisus genomes identifies genomospecies features secretion systems and novel plasmids and their association with severe ulcerative colitis
    Microbial genomics, 2020
    Co-Authors: Fang Liu, Stephen M Riordan, Ruiting Lan, Seul A Lee, Alfred Tay, Siying Chen, Lu Liu, Laurence Don Wai Luu, Li Zhang
    Abstract:

    Campylobacter Concisus is an emerging enteric pathogen that is associated with several gastrointestinal diseases, such as inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). Currently, only three complete C. Concisus genomes are available and more complete C. Concisus genomes are needed in order to better understand the genomic features and pathogenicity of this emerging pathogen. DNA extracted from 22 C. Concisus strains were subjected to Oxford Nanopore genome sequencing. Complete genome assembly was performed using Nanopore genome data in combination with previously reported short-read Illumina data. Genome features of complete C. Concisus genomes were analysed using bioinformatic tools. The enteric disease associations of C. Concisus plasmids were examined using 239 C. Concisus strains and confirmed using PCRs. Proteomic analysis was used to examine T6SS secreted proteins. We successfully obtained 13 complete C. Concisus genomes in this study. Analysis of 16 complete C. Concisus genomes (3 from public databases) identified multiple novel plasmids. pSma1 plasmid was found to be associated with severe UC. Sec-SRP, Tat and T6SS were found to be the main secretion systems in C. Concisus and proteomic data showed a functional T6SS despite the lack of ClpV. T4SS was found in 25% of complete C. Concisus genomes. This study also found that GS2 strains had larger genomes and higher GC content than GS1 strains and more often had plasmids. In conclusion, this study provides fundamental genomic data for understanding C. Concisus plasmids, genomospecies features, evolution, secretion systems and pathogenicity.

  • Analyses of energy metabolism and stress defence provide insights into Campylobacter Concisus growth and pathogenicity
    Gut Pathogens, 2020
    Co-Authors: Melissa Yeow, Stephen M Riordan, Fang Liu, Timothy J. Williams, Li Zhang
    Abstract:

    Campylobacter Concisus is an emerging enteric pathogen that is associated with inflammatory bowel disease. Previous studies demonstrated that C. Concisus is non-saccharolytic and hydrogen gas (H_2) is a critical factor for C. Concisus growth. In order to understand the molecular basis of the non-saccharolytic and H_2-dependent nature of C. Concisus growth, in this study we examined the pathways involving energy metabolism and oxidative stress defence in C. Concisus . Bioinformatic analysis of C. Concisus genomes in comparison with the well-studied enteric pathogen Campylobacter jejuni was performed. This study found that C. Concisus lacks a number of key enzymes in glycolysis, including glucokinase and phosphofructokinase, and the oxidative pentose phosphate pathway. C. Concisus has an incomplete tricarboxylic acid cycle, with no identifiable succinyl-CoA synthase or fumarate hydratase. C. Concisus was inferred to use fewer amino acids and have fewer candidate substrates as electron donors and acceptors compared to C. jejuni . The addition of DMSO or fumarate to media resulted in significantly increased growth of C. Concisus in the presence of H_2 as an electron donor, demonstrating that both can be used as electron acceptors. Catalase, an essential enzyme for oxidative stress defence in C. jejuni , and various nitrosative stress enzymes, were not found in the C. Concisus genome. Overall, C. Concisus is inferred to have a non-saccharolytic metabolism in which H_2 is central to energy conservation, and a narrow selection of carboxylic acids and amino acids can be utilised as organic substrates. In conclusion, this study provides a molecular basis for the non-saccharolytic and hydrogen-dependent nature of C. Concisus energy metabolism pathways, which provides insights into the growth requirements and pathogenicity of this species.

  • detection of il 18 and il 1β protein and mrna in human oral epithelial cells induced by Campylobacter Concisus strains
    Biochemical and Biophysical Research Communications, 2019
    Co-Authors: Jieqiong Chen, Fang Liu, Stephen M Riordan, Seul A Lee, Siying Chen, Xiaoyan Zhou, Lu Liu, Li Zhang
    Abstract:

    Abstract Campylobacter Concisus is an emerging bacterial pathogen that may play a role in the development of inflammatory bowel disease and oral inflammatory conditions such as periodontal disease. To elucidate the role and pathogenic mechanisms of C. Concisus in contributing to oral inflammation, this study examined the production of IL-1 family proinflammatory cytokines IL-18 and IL-1β in oral epithelial cells induced by C. Concisus strains using enzyme-linked immunosorbent assay (ELISA), Western-blot and quantitative real-time PCR. C. Concisus increased the mRNA levels of IL-18 and IL-1β in oral epithelial cells. Furthermore, a large amount of IL-18 in the supernatants of oral epithelial cells infected with C. Concisus strains was detected by ELISA, and various experiments demonstrated that this positive signal was derived from C. Concisus bacterium. The findings that C. Concisus upregulated IL-18 and IL-1β in oral epithelial cells from this study support a role of C. Concisus in oral inflammatory diseases. Furthermore, the finding that C. Concisus released a molecule that was strongly cross-reactive to anti-human IL-18 monoclonal antibodies suggests that in future studies examining cytokines induced by bacterial microbes, a bacterium control should be included.

  • refolding characterization and preliminary x ray crystallographic studies on the Campylobacter Concisus plasmid encoded secreted protein csep1p associated with crohn s disease
    Crystals, 2018
    Co-Authors: Mohammad M Rahman, Li Zhang, Bradley Goff, Anna Roujeinikova
    Abstract:

    Colonization of Campylobacter Concisus in the gastrointestinal tract can lead to the development of inflammatory bowel disease (IBD). Plasmid-encoded C. Concisus-secreted protein 1 (Csep1p) was recently identified as a putative pathogenicity marker associated with active Crohn’s disease, a clinical form of IBD. Csep1p shows no significant full-length sequence similarity to proteins of known structure, and its role in pathogenesis is not yet known. This study reports a method for extraction of recombinantly expressed Csep1p from Escherichia coli inclusion bodies, refolding, and purification to produce crystallizable protein. Purified recombinant Csep1p behaved as a monomer in solution. Crystals of Csep1p were grown by the hanging drop vapour diffusion method, using polyethylene glycol (PEG) 4000 as the precipitating agent. A complete data set has been collected to 1.4 A resolution, using cryocooling conditions and synchrotron radiation. The crystals belong to space group P62 or P64, with unit cell parameters a = b = 85.8, c = 55.2 A, α = β = 90, and γ = 120°. The asymmetric unit appears to contain one subunit, corresponding to a packing density of 2.47 A3 Da−1.

  • The Clinical Importance of Campylobacter Concisus and Other Human Hosted Campylobacter Species.
    Frontiers in cellular and infection microbiology, 2018
    Co-Authors: Fang Liu, Yiming Wang, Li Zhang
    Abstract:

    Historically, Campylobacteriosis has been considered to be zoonotic; the Campylobacter species that cause human acute intestinal disease such as Campylobacter jejuni and Campylobacter coli originate from animals. Over the past decade, studies on human hosted Campylobacter species strongly suggest that Campylobacter Concisus plays a role in the development of inflammatory bowel disease (IBD). C. Concisus primarily colonizes the human oral cavity and some strains can be translocated to the intestinal tract. Genome analysis of C. Concisus strains isolated from saliva samples has identified a bacterial marker that is associated with active Crohn's disease (one major form of IBD). In addition to C. Concisus, humans are also colonized by a number of other Campylobacter species, most of which are in the oral cavity. Here we review the most recent advancements on C. Concisus and other human hosted Campylobacter species including their clinical relevance, transmission, virulence factors, disease associated genes, interactions with the human immune system and pathogenic mechanisms.

Henrik Nielsen - One of the best experts on this subject based on the ideXlab platform.

  • High genetic diversity in Campylobacter Concisus isolates from patients with microscopic colitis
    Gut Pathogens, 2021
    Co-Authors: Marta Emilie Yde Aagaard, Henrik Nielsen, Karina Frahm Kirk, Hans Linde Nielsen
    Abstract:

    The emerging intestinal pathogen Campylobacter Concisus has been associated with prolonged diarrhoea and classic inflammatory bowel diseases (IBD) and was recently also linked with microscopic colitis (MC). Previous reports have observed a high genetic diversity within isolates from diarrhoeic and IBD patients and from healthy controls (HC), and division of isolates into two major genomospecies (GS1 and GS2). The aim of this study was to describe genetic diversity in 80 recently cultivated MC biopsy and faecal isolates of C. Concisus by multi-locus sequence typing (MLST); and to compare the phylogenetic relatedness to 102 isolates from diarrhoeic and IBD patients and HCs by k-mer-based distance estimation. MLST revealed high genetic diversity in MC isolates with 72 novel sequence types. K-mer divided MC isolates into two distinct clusters (cluster 1 n = 21, cluster 2 n = 49), with a significantly higher prevalence of cluster 2 isolates in biopsies than in faeces, p = 0.009. K-mer divided the 182 isolates into two major phylogenetic clusters: cluster 1 (GS1 isolates) and cluster 2 (GS2 isolates), which further differentiated into three subgroups. Cluster 1 and the three cluster 2 subgroups were each distinctive in mean genome size and GC count. Isolates from all disease phenotypes were present in cluster 1 and cluster 2 subgroup 2 and 3, whereas cluster 2 subgroup 1 only contained isolates restricted to patients with ulcerative colitis (n = 10) and HC (n = 4).

  • Campylobacter Concisus is prevalent in the gastrointestinal tract of patients with microscopic colitis
    Scandinavian Journal of Gastroenterology, 2020
    Co-Authors: Marta Emilie Yde Aagaard, Hans Linde Nielsen, Karina Frahm Kirk, Irene Harder Tarpgaard, Jesper Bach Hansen, Henrik Nielsen
    Abstract:

    Microscopic colitis (MC) is potentially induced by an inflammatory reaction to a luminal gut factor. The emerging pathogen Campylobacter Concisus is associated with prolonged diarrhoea and subseque...

  • high risk of microscopic colitis after Campylobacter Concisus infection population based cohort study
    Gut, 2020
    Co-Authors: Hans Linde Nielsen, Michael Dalagerpedersen, Henrik Nielsen
    Abstract:

    Objective Microscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter Concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test. Design We identified patients with a first-time positive stool culture with C. Concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons. Results We identified 962 patients with C. Concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. Concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively. Conclusion A high risk of MC was observed following C. Concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.

  • risk of inflammatory bowel disease after Campylobacter jejuni and Campylobacter Concisus infection a population based cohort study
    Scandinavian Journal of Gastroenterology, 2019
    Co-Authors: Hans Linde Nielsen, Michael Dalagerpedersen, Henrik Nielsen
    Abstract:

    Objectives: In this population-based cohort study, we aimed to examine the risk of IBD following a positive stool culture with Campylobacter jejuni or Campylobacter Concisus, as well as following culture-negative stool testing. Materials and methods: Patients with a first-time positive stool culture with C. jejuni or C. Concisus, as well as negative stool testing, from 2009 through 2013 in North Denmark Region, Denmark, were identified. Patients diagnosed with IBD during follow-up (to 1 March 2018) were identified using national registries. For each case, we selected ten population comparisons matched by age, gender, and calendar-time. Results: We identified 1693 patients with C. jejuni, 910 C. Concisus-positive patients, and 11,383 patients with culture-negative stools. During the first year of follow-up C. jejuni-positive patients had higher risk of IBD (HR 2.2, 95% CI 1.3-3.7) compared to population comparisons, but not after exclusion of the first year (HR 1.1, 95% CI 0.5-2.3). Campylobacter Concisus-positive patients and culture-negative patients had similar risk of IBD (HR 12.9, 95% CI 7.2-22.9 and HR 8.7, 95% CI 7.5-10.2), during the first year, which decreased to (HR 3.3, 95% CI 1.3-8.5 and HR 3.2, 95% CI 2.6-4.0) after exclusion of the first year. Conclusions: This study does not support exposure of C. jejuni or C. Concisus infection as a causal trigger in subsequent development of IBD, since culture-negative patients had similar risk for IBD on long term follow-up. Additional studies including C. Concisus exposures for an evaluation of the specific risk of IBD are needed.

  • motility and biofilm formation of the emerging gastrointestinal pathogen Campylobacter Concisus differs under microaerophilic and anaerobic environments
    Gut microbes, 2019
    Co-Authors: Sandra Ovesen, Hans Linde Nielsen, Henrik Nielsen, Karina Frahm Kirk, Juliana Durack, Susan V Lynch
    Abstract:

    Campylobacter Concisus has been isolated from patients with gastroenteritis and inflammatory bowel disease (IBD), as well as healthy subjects. While strain differences may plausibly explain virulence differentials, an alternative hypothesis posits that the pathogenic potential of this species may depend on altered ecosystem conditions in the inflamed gut. One potential difference is oxygen availability, which is frequently increased under conditions of inflammation and is known to regulate bacterial virulence. Hence, we hypothesized that oxygen influences C. Concisus physiology. We therefore characterized the effect of microaerophilic or anaerobic environments on C. Concisus motility and biofilm formation, two important determinants of host colonization and dissemination. C. Concisus isolates (n = 46) sourced from saliva, gut mucosal biopsies and feces of patients with IBD (n = 23), gastroenteritis (n = 8) and healthy subjects (n = 13), were used for this study. Capacity to form biofilms was determined using crystal violet assay, while assessment of dispersion through soft agar permitted motility to be assessed. No association existed between GI disease and either motility or biofilm forming capacity. Oral isolates exhibited significantly greater capacity for biofilm formation compared to fecal isolates (p<0.03), and showed a strong negative correlation between motility and biofilm formation (r = -0.7; p = 0.01). Motility significantly increased when strains were cultured under microaerophilic compared to anaerobic conditions (p<0.001). Increased biofilm formation under microaerophillic conditions was also observed for a subset of isolates. Hence, differences in oxygen availability appear to influence key physiological aspects of the opportunistic gastrointestinal pathogen C. Concisus.

Hans Linde Nielsen - One of the best experts on this subject based on the ideXlab platform.

  • High genetic diversity in Campylobacter Concisus isolates from patients with microscopic colitis
    Gut Pathogens, 2021
    Co-Authors: Marta Emilie Yde Aagaard, Henrik Nielsen, Karina Frahm Kirk, Hans Linde Nielsen
    Abstract:

    The emerging intestinal pathogen Campylobacter Concisus has been associated with prolonged diarrhoea and classic inflammatory bowel diseases (IBD) and was recently also linked with microscopic colitis (MC). Previous reports have observed a high genetic diversity within isolates from diarrhoeic and IBD patients and from healthy controls (HC), and division of isolates into two major genomospecies (GS1 and GS2). The aim of this study was to describe genetic diversity in 80 recently cultivated MC biopsy and faecal isolates of C. Concisus by multi-locus sequence typing (MLST); and to compare the phylogenetic relatedness to 102 isolates from diarrhoeic and IBD patients and HCs by k-mer-based distance estimation. MLST revealed high genetic diversity in MC isolates with 72 novel sequence types. K-mer divided MC isolates into two distinct clusters (cluster 1 n = 21, cluster 2 n = 49), with a significantly higher prevalence of cluster 2 isolates in biopsies than in faeces, p = 0.009. K-mer divided the 182 isolates into two major phylogenetic clusters: cluster 1 (GS1 isolates) and cluster 2 (GS2 isolates), which further differentiated into three subgroups. Cluster 1 and the three cluster 2 subgroups were each distinctive in mean genome size and GC count. Isolates from all disease phenotypes were present in cluster 1 and cluster 2 subgroup 2 and 3, whereas cluster 2 subgroup 1 only contained isolates restricted to patients with ulcerative colitis (n = 10) and HC (n = 4).

  • Campylobacter Concisus is prevalent in the gastrointestinal tract of patients with microscopic colitis
    Scandinavian Journal of Gastroenterology, 2020
    Co-Authors: Marta Emilie Yde Aagaard, Hans Linde Nielsen, Karina Frahm Kirk, Irene Harder Tarpgaard, Jesper Bach Hansen, Henrik Nielsen
    Abstract:

    Microscopic colitis (MC) is potentially induced by an inflammatory reaction to a luminal gut factor. The emerging pathogen Campylobacter Concisus is associated with prolonged diarrhoea and subseque...

  • high risk of microscopic colitis after Campylobacter Concisus infection population based cohort study
    Gut, 2020
    Co-Authors: Hans Linde Nielsen, Michael Dalagerpedersen, Henrik Nielsen
    Abstract:

    Objective Microscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter Concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test. Design We identified patients with a first-time positive stool culture with C. Concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons. Results We identified 962 patients with C. Concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. Concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively. Conclusion A high risk of MC was observed following C. Concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.

  • risk of inflammatory bowel disease after Campylobacter jejuni and Campylobacter Concisus infection a population based cohort study
    Scandinavian Journal of Gastroenterology, 2019
    Co-Authors: Hans Linde Nielsen, Michael Dalagerpedersen, Henrik Nielsen
    Abstract:

    Objectives: In this population-based cohort study, we aimed to examine the risk of IBD following a positive stool culture with Campylobacter jejuni or Campylobacter Concisus, as well as following culture-negative stool testing. Materials and methods: Patients with a first-time positive stool culture with C. jejuni or C. Concisus, as well as negative stool testing, from 2009 through 2013 in North Denmark Region, Denmark, were identified. Patients diagnosed with IBD during follow-up (to 1 March 2018) were identified using national registries. For each case, we selected ten population comparisons matched by age, gender, and calendar-time. Results: We identified 1693 patients with C. jejuni, 910 C. Concisus-positive patients, and 11,383 patients with culture-negative stools. During the first year of follow-up C. jejuni-positive patients had higher risk of IBD (HR 2.2, 95% CI 1.3-3.7) compared to population comparisons, but not after exclusion of the first year (HR 1.1, 95% CI 0.5-2.3). Campylobacter Concisus-positive patients and culture-negative patients had similar risk of IBD (HR 12.9, 95% CI 7.2-22.9 and HR 8.7, 95% CI 7.5-10.2), during the first year, which decreased to (HR 3.3, 95% CI 1.3-8.5 and HR 3.2, 95% CI 2.6-4.0) after exclusion of the first year. Conclusions: This study does not support exposure of C. jejuni or C. Concisus infection as a causal trigger in subsequent development of IBD, since culture-negative patients had similar risk for IBD on long term follow-up. Additional studies including C. Concisus exposures for an evaluation of the specific risk of IBD are needed.

  • motility and biofilm formation of the emerging gastrointestinal pathogen Campylobacter Concisus differs under microaerophilic and anaerobic environments
    Gut microbes, 2019
    Co-Authors: Sandra Ovesen, Hans Linde Nielsen, Henrik Nielsen, Karina Frahm Kirk, Juliana Durack, Susan V Lynch
    Abstract:

    Campylobacter Concisus has been isolated from patients with gastroenteritis and inflammatory bowel disease (IBD), as well as healthy subjects. While strain differences may plausibly explain virulence differentials, an alternative hypothesis posits that the pathogenic potential of this species may depend on altered ecosystem conditions in the inflamed gut. One potential difference is oxygen availability, which is frequently increased under conditions of inflammation and is known to regulate bacterial virulence. Hence, we hypothesized that oxygen influences C. Concisus physiology. We therefore characterized the effect of microaerophilic or anaerobic environments on C. Concisus motility and biofilm formation, two important determinants of host colonization and dissemination. C. Concisus isolates (n = 46) sourced from saliva, gut mucosal biopsies and feces of patients with IBD (n = 23), gastroenteritis (n = 8) and healthy subjects (n = 13), were used for this study. Capacity to form biofilms was determined using crystal violet assay, while assessment of dispersion through soft agar permitted motility to be assessed. No association existed between GI disease and either motility or biofilm forming capacity. Oral isolates exhibited significantly greater capacity for biofilm formation compared to fecal isolates (p<0.03), and showed a strong negative correlation between motility and biofilm formation (r = -0.7; p = 0.01). Motility significantly increased when strains were cultured under microaerophilic compared to anaerobic conditions (p<0.001). Increased biofilm formation under microaerophillic conditions was also observed for a subset of isolates. Hence, differences in oxygen availability appear to influence key physiological aspects of the opportunistic gastrointestinal pathogen C. Concisus.

Hazel M. Mitchell - One of the best experts on this subject based on the ideXlab platform.

  • Campylobacter Concisus pathotypes induce distinct global responses in intestinal epithelial cells
    Scientific Reports, 2016
    Co-Authors: Nandan P Deshpande, Hazel M. Mitchell, Nidhi Sodhi, Stephen M Riordan, Marc R Wilkins, Natalia Castaño-rodríguez, Emily Bainbridge, Nadeem O. Kaakoush
    Abstract:

    The epithelial response to the opportunistic pathogen Campylobacter Concisus is poorly characterised. Here, we assessed the intestinal epithelial responses to two C. Concisus strains with different virulence characteristics in Caco-2 cells using RNAseq, and validated a subset of the response using qPCR arrays. C. Concisus strains induced distinct response patterns from intestinal epithelial cells, with the toxigenic strain inducing a significantly more amplified response. A range of cellular functions were significantly regulated in a strain-specific manner, including epithelial-to-mesenchymal transition (NOTCH and Hedgehog), cytoskeletal remodeling, tight junctions, inflammatory responses and autophagy. Pattern recognition receptors were regulated, including TLR3 and IFI16 , suggesting that nucleic acid sensing was important for epithelial recognition of C. Concisus . C. Concisus zonula occludens toxin (ZOT) was expressed and purified, and the epithelial response to the toxin was analysed using RNAseq. ZOT upregulated PAR2 expression, as well as processes related to tight junctions and cytoskeletal remodeling. C. Concisus ZOT also induced upregulation of TLR3 , pro-inflammatory cytokines IL6 , IL8 and chemokine CXCL16 , as well as the executioner caspase CASP7 . Here, we characterise distinct global epithelial responses to C. Concisus strains, and the virulence factor ZOT, and provide novel information on mechanisms by which this bacterium may affect the host.

  • Campylobacter Concisus utilizes blood but not short chain fatty acids despite showing associations with firmicutes taxa
    Microbiology, 2016
    Co-Authors: Nadeem O. Kaakoush, Andrew S Day, Steven T Leach, Daniel A Lemberg, Donald S Thomas, Mahmoud M Ruzayqat, David Lynch, Hazel M. Mitchell
    Abstract:

    Campylobacter Concisus is a member of the oral microbiota that has been associated with the development of inflammatory bowel diseases. However, the role of the bacterium in disease aetiology remains poorly understood. Here, we examine optimal conditions for the growth of C. Concisus, and the pathogenic potential of this bacterium in human gastrointestinal cells from the upper tract. Further, the presence of C. Concisus in the lower tract of Crohn's disease (CD) patients undergoing therapy is observed, and the associations of C. Concisus with the abundance of other microbial taxa and compounds they produce are evaluated. C. Concisus strains had the ability to tolerate moderate levels of acidity, adhere to and invade esophageal and gastric cells; however, these properties did not correlate with their pathogenic potential in intestinal cells. The presence of the bacterium in the lower gut of CD patients was associated with an increased relative abundance of Faecalibacterium and Lachnospiraceae incertae sedis. Short chain fatty acids that can be produced by these microbial species did not appear to be responsible for this association. However, we identified genetic similarity between C. Concisus and Firmicutes, specifically within aspartate and glutamate racemases. The potential pathogenesis of C. Concisus in the upper gastrointestinal tract, and the responsiveness of the bacterium to therapy in a subset of CD patients warrant further investigation into whether this bacterium has a causal role in disease or its presence is incidental.

  • Campylobacter Concisus pathotypes are present at significant levels in patients with gastroenteritis
    Journal of Medical Microbiology, 2016
    Co-Authors: Alexander Underwood, Nadeem O. Kaakoush, Nidhi Sodhi, Juan Merif, Way Seah Lee, Stephen M Riordan, William D Rawlinson, Hazel M. Mitchell
    Abstract:

    Given that Campylobacter jejuni is recognized as the most common cause of bacterial gastroenteritis worldwide, recent findings showing comparable levels of Campylobacter Concisus in patients with gastroenteritis would suggest that this bacterium is clinically important. The prevalence and abundance of Campylobacter Concisus in stool samples collected from patients with acute gastroenteritis was examined using quantitative real-time PCR. The associated virulence determinants exotoxin 9 and zonula occludens toxin DNA were detected for Campylobacter Concisus-infected samples using real-time PCR. Campylobacter Concisus was detected at high prevalence in patients with gastroenteritis (49.7 %), higher than that observed for Campylobacter jejuni (∼5 %). The levels of Campylobacter Concisus were putatively classified into clinically relevant and potentially transient subgroups based on a threshold developed using Campylobacter jejuni levels, as the highly sensitive real-time PCR probably detected transient passage of the bacterium from the oral cavity. A total of 18 % of patients were found to have clinically relevant levels of Campylobacter Concisus, a significant number of which also had high levels of one of the virulence determinants. Of these patients, 78 % were found to have no other gastrointestinal pathogen identified in the stool, which strongly suggests a role for Campylobacter Concisus in the aetiology of gastroenteritis in these patients. These results emphasize the need for diagnostic laboratories to employ identification protocols for emerging Campylobacter species. Clinical follow-up in patients presenting with high levels of Campylobacter Concisus in the intestinal tract is needed, given that it has been associated with more chronic sequelae.

  • transcriptomic and proteomic analyses reveal key innate immune signatures in the host response to the gastrointestinal pathogen Campylobacter Concisus
    Infection and Immunity, 2015
    Co-Authors: Nadeem O. Kaakoush, Si Ming Man, Nandan P Deshpande, Marc R Wilkins, Mark J Raftery, Jose A Burgosportugal, Faisal Asghar Khattak, Hazel M. Mitchell
    Abstract:

    Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter Concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. Concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. Concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. Concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. Concisus, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. Concisus.

  • immunoglobulin g response in patients with Campylobacter Concisus diarrhea
    18th International Workshop on Campylobacter Helicobacter and Related Organisms, 2015
    Co-Authors: Hans Linde Nielsen, Nadeem O. Kaakoush, Hazel M. Mitchell, Henrik Nielsen
    Abstract:

    Limited information is available on the systemic immunoglobulin response in patients infected with the emerging pathogen Campylobacter Concisus. The aim of the present study was to detect anti-C. Concisus antibodies in serum of 88 patients with C. Concisus gastroenteritis. Specific IgG antibodies to C. Concisus were measured in serum using an in-house enzyme-linked immunosorbent assay, and pooled donor serum was used as a control. The mean optical density was 0.135 (SEM: 0.020) for the 88 adult patients and 0.100 (SEM: 0.011) in controls. When using an optical density value equal to the mean +3 SEM for the control serum, 22 (25%) C. Concisus-positive patients had increased IgG antibodies. Patients with high IgG levels more often reported headache, and they had a trend toward more mucus in stools, whereas IgG levels were unrelated to age, duration of diarrhea, number of stools per day, and weight loss.

Stephen M Riordan - One of the best experts on this subject based on the ideXlab platform.

  • analysis of complete Campylobacter Concisus genomes identifies genomospecies features secretion systems and novel plasmids and their association with severe ulcerative colitis
    Microbial genomics, 2020
    Co-Authors: Fang Liu, Stephen M Riordan, Ruiting Lan, Seul A Lee, Alfred Tay, Siying Chen, Lu Liu, Laurence Don Wai Luu, Li Zhang
    Abstract:

    Campylobacter Concisus is an emerging enteric pathogen that is associated with several gastrointestinal diseases, such as inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). Currently, only three complete C. Concisus genomes are available and more complete C. Concisus genomes are needed in order to better understand the genomic features and pathogenicity of this emerging pathogen. DNA extracted from 22 C. Concisus strains were subjected to Oxford Nanopore genome sequencing. Complete genome assembly was performed using Nanopore genome data in combination with previously reported short-read Illumina data. Genome features of complete C. Concisus genomes were analysed using bioinformatic tools. The enteric disease associations of C. Concisus plasmids were examined using 239 C. Concisus strains and confirmed using PCRs. Proteomic analysis was used to examine T6SS secreted proteins. We successfully obtained 13 complete C. Concisus genomes in this study. Analysis of 16 complete C. Concisus genomes (3 from public databases) identified multiple novel plasmids. pSma1 plasmid was found to be associated with severe UC. Sec-SRP, Tat and T6SS were found to be the main secretion systems in C. Concisus and proteomic data showed a functional T6SS despite the lack of ClpV. T4SS was found in 25% of complete C. Concisus genomes. This study also found that GS2 strains had larger genomes and higher GC content than GS1 strains and more often had plasmids. In conclusion, this study provides fundamental genomic data for understanding C. Concisus plasmids, genomospecies features, evolution, secretion systems and pathogenicity.

  • Analyses of energy metabolism and stress defence provide insights into Campylobacter Concisus growth and pathogenicity
    Gut Pathogens, 2020
    Co-Authors: Melissa Yeow, Stephen M Riordan, Fang Liu, Timothy J. Williams, Li Zhang
    Abstract:

    Campylobacter Concisus is an emerging enteric pathogen that is associated with inflammatory bowel disease. Previous studies demonstrated that C. Concisus is non-saccharolytic and hydrogen gas (H_2) is a critical factor for C. Concisus growth. In order to understand the molecular basis of the non-saccharolytic and H_2-dependent nature of C. Concisus growth, in this study we examined the pathways involving energy metabolism and oxidative stress defence in C. Concisus . Bioinformatic analysis of C. Concisus genomes in comparison with the well-studied enteric pathogen Campylobacter jejuni was performed. This study found that C. Concisus lacks a number of key enzymes in glycolysis, including glucokinase and phosphofructokinase, and the oxidative pentose phosphate pathway. C. Concisus has an incomplete tricarboxylic acid cycle, with no identifiable succinyl-CoA synthase or fumarate hydratase. C. Concisus was inferred to use fewer amino acids and have fewer candidate substrates as electron donors and acceptors compared to C. jejuni . The addition of DMSO or fumarate to media resulted in significantly increased growth of C. Concisus in the presence of H_2 as an electron donor, demonstrating that both can be used as electron acceptors. Catalase, an essential enzyme for oxidative stress defence in C. jejuni , and various nitrosative stress enzymes, were not found in the C. Concisus genome. Overall, C. Concisus is inferred to have a non-saccharolytic metabolism in which H_2 is central to energy conservation, and a narrow selection of carboxylic acids and amino acids can be utilised as organic substrates. In conclusion, this study provides a molecular basis for the non-saccharolytic and hydrogen-dependent nature of C. Concisus energy metabolism pathways, which provides insights into the growth requirements and pathogenicity of this species.

  • detection of il 18 and il 1β protein and mrna in human oral epithelial cells induced by Campylobacter Concisus strains
    Biochemical and Biophysical Research Communications, 2019
    Co-Authors: Jieqiong Chen, Fang Liu, Stephen M Riordan, Seul A Lee, Siying Chen, Xiaoyan Zhou, Lu Liu, Li Zhang
    Abstract:

    Abstract Campylobacter Concisus is an emerging bacterial pathogen that may play a role in the development of inflammatory bowel disease and oral inflammatory conditions such as periodontal disease. To elucidate the role and pathogenic mechanisms of C. Concisus in contributing to oral inflammation, this study examined the production of IL-1 family proinflammatory cytokines IL-18 and IL-1β in oral epithelial cells induced by C. Concisus strains using enzyme-linked immunosorbent assay (ELISA), Western-blot and quantitative real-time PCR. C. Concisus increased the mRNA levels of IL-18 and IL-1β in oral epithelial cells. Furthermore, a large amount of IL-18 in the supernatants of oral epithelial cells infected with C. Concisus strains was detected by ELISA, and various experiments demonstrated that this positive signal was derived from C. Concisus bacterium. The findings that C. Concisus upregulated IL-18 and IL-1β in oral epithelial cells from this study support a role of C. Concisus in oral inflammatory diseases. Furthermore, the finding that C. Concisus released a molecule that was strongly cross-reactive to anti-human IL-18 monoclonal antibodies suggests that in future studies examining cytokines induced by bacterial microbes, a bacterium control should be included.

  • the growth and protein expression of inflammatory bowel disease associated Campylobacter Concisus is affected by the derivatives of the food additive fumaric acid
    Frontiers in Microbiology, 2018
    Co-Authors: Fang Liu, Stephen M Riordan, Michael Grimm, Hoyul Lee, Rupert W Leong, Soe F Yap, Li Zhang
    Abstract:

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract with multifactorial etiology. Both dietary factors and the microbe Campylobacter Concisus have been found to be associated with the condition. The current study examined the effects of sodium fumarate, a neutralized product of the food additives fumaric acid and monosodium fumarate when in the intestinal environment, on the growth of C. Concisus to determine the effects of these food additives on IBD-associated bacterial species. Through culture methods and quantification, it was found that neutralized fumaric acid, neutralized monosodium fumarate, and sodium fumarate increased the growth of C. Concisus, with the greatest increase in growth at a concentration of 0.4%. Further examination of 50 C. Concisus strains on media with added sodium fumarate showed that greatest growth was also achieved at a concentration of 0.4%. At a concentration of 2% sodium fumarate, all strains examined displayed less growth in comparison with those cultured on media without sodium fumarate. Using mass spectrometry, multiple C. Concisus proteins showed significant differential expression when cultured on media with and without 0.4% sodium fumarate. The findings presented suggest that patients with IBD should consider avoiding excessive consumption of foods with fumaric acid or its sodium salts, and that the addition of 0.4% sodium fumarate alone to media may assist in the isolation of C. Concisus from clinical samples.

  • genomic analysis of oral Campylobacter Concisus strains identified a potential bacterial molecular marker associated with active crohn s disease
    Emerging microbes & infections, 2018
    Co-Authors: Fang Liu, Stephen M Riordan, Michael Grimm, Mark M Tanaka, Sophie Octavia, Ruiting Lan, Heung Kit Leslie Chung, Chin Yen Alfred Tay, Rupert W Leong, Susan J Connor
    Abstract:

    Campylobacter Concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC). C. Concisus consists of two genomospecies (GS) and diverse strains. This study aimed to identify molecular markers to differentiate commensal and IBD-associated C. Concisus strains. The genomes of 63 oral C. Concisus strains isolated from patients with IBD and healthy controls were examined, of which 38 genomes were sequenced in this study. We identified a novel secreted enterotoxin B homologue, Csep1. The csep1 gene was found in 56% of GS2 C. Concisus strains, presented in the plasmid pICON or the chromosome. A six-nucleotide insertion at the position 654–659 bp in csep1 (csep1-6bpi) was found. The presence of csep1-6bpi in oral C. Concisus strains isolated from patients with active CD (47%, 7/15) was significantly higher than that in strains from healthy controls (0/29, P = 0.0002), and the prevalence of csep1-6bpi positive C. Concisus strains was significantly higher in patients with active CD (67%, 4/6) as compared to healthy controls (0/23, P = 0.0006). Proteomics analysis detected the Csep1 protein. A csep1 gene hot spot in the chromosome of different C. Concisus strains was found. The pICON plasmid was only found in GS2 strains isolated from the two relapsed CD patients with small bowel complications. This study reports a C. Concisus molecular marker (csep1-6bpi) that is associated with active CD.