scholarly journals Propionic acid promotes the virulent phenotype of Crohn’s disease-associated adherent-invasive Escherichia coli

2018 ◽  
Author(s):  
Michael J. Ormsby ◽  
Síle A. Johnson ◽  
Lynsey M. Meikle ◽  
Robert J. Goldstone ◽  
Anne McIntosh ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Propionic Acid ◽  
Biofilm Formation ◽  
Food Production ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Phenotypic Changes

AbstractThe short chain fatty acid propionic acid (PA) is a bacteria-derived human intestinal antimicrobial and immune modulator used widely in Western food production and agriculture. Here we examine the effect of PA on the pathogenicity of the Crohn’s disease-associated microbe, adherent-invasive Escherichia coli (AIEC). Passage of AIEC through a murine model, where the low intestinal PA levels were increased to replicate those of the human intestine, led to the recovery of AIEC post-infection that had significantly increased virulence. These phenotypic changes, including increased adhesion to intestinal epithelial cells and biofilm formation, could be replicated in AIEC in vitro through exposure to PA alone. This in vitro exposure of AIEC to PA fundamentally changed AIEC virulence, with strains exposed to PA in vitro subsequently persisting at 20-fold higher levels in a murine model compared to non-exposed strains. RNA-sequencing identified the transcriptional changes in AIEC in response to PA with upregulation of genes involved in biofilm formation, stress responses, metabolism, membrane integrity and alternative carbon source utilisation. These PA induced changes in virulence could be replicated in a number of E. coli isolates from Crohn’s disease patients. Finally, removal of the PA selective pressure was sufficient to reverse these phenotypic changes. Our data indicate that exposure of AIEC to PA evolves bacteria that are both resistant to this natural human intestinal antimicrobial and increasingly virulent in its presence.ImportanceExposure to propionic acid, an intestinal short chain fatty acid and commonly used antimicrobial in Western food production, induces significant virulence associated phenotypic changes in adherent-invasive Escherichia coli (AIEC).

scholarly journals Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce granulomas in vitro

2007 ◽  
Vol 9 (5) ◽  
pp. 1252-1261 ◽  
Author(s):  
Sonia Meconi ◽  
Alain Vercellone ◽  
Florence Levillain ◽  
Bruno Payré ◽  
Talal Al Saati ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease

scholarly journals Propionic Acid Promotes the Virulent Phenotype of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli

Cell Reports ◽  
2020 ◽  
Vol 30 (7) ◽  
pp. 2297-2305.e5 ◽  
Author(s):  
Michael J. Ormsby ◽  
Síle A. Johnson ◽  
Nuria Carpena ◽  
Lynsey M. Meikle ◽  
Robert J. Goldstone ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Propionic Acid ◽  
Virulent Phenotype

scholarly journals Development of Heptylmannoside-Based Glycoconjugate Antiadhesive Compounds against Adherent-Invasive Escherichia coli Bacteria Associated with Crohn's Disease

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Adeline Sivignon ◽  
Xibo Yan ◽  
Dimitri Alvarez Dorta ◽  
Richard Bonnet ◽  
Julie Bouckaert ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Type 1 Pili

ABSTRACTThe ileal lesions of Crohn's disease (CD) patients are colonized by adherent-invasiveEscherichia coli(AIEC) bacteria. These bacteria adhere to mannose residues expressed by CEACAM6 on host cells in a type 1 pilus-dependent manner. In this study, we investigated different antagonists of FimH, the adhesin of type 1 pili, for their ability to block AIEC adhesion to intestinal epithelial cells (IEC). Monovalent and multivalent derivatives ofn-heptyl α-d-mannoside (HM), a nanomolar antagonist of FimH, were testedin vitroin IEC infected with the AIEC LF82 strain andin vivoby oral administration to CEACAM6-expressing mice infected with LF82 bacteria.In vitro, multivalent derivatives were more potent than the monovalent derivatives, with a gain of efficacy superior to their valencies, probably owing to their ability to form bacterial aggregates. Of note, HM and the multi-HM glycoconjugates exhibited lower efficacyin vivoin decreasing LF82 gut colonization. Interestingly, HM analogues functionalized with an isopropylamide (1A-HM) or β-cyclodextrin pharmacophore at the end of the heptyl tail (1CD-HM) exerted beneficial effectsin vivo. These two compounds strongly decreased the amount of LF82 bacteria in the feces of mice and that of bacteria associated with the gut mucosa when administered orally at a dose of 10 mg/kg of body weight after infection. Importantly, signs of colitis and intestinal inflammation induced by LF82 infection were also prevented. These results highlight the potential of the antiadhesive compounds to treat CD patients abnormally colonized by AIEC bacteria and point to an alternative to the current approach focusing on blocking proinflammatory mediators.IMPORTANCECurrent treatments for Crohn's disease (CD), including immunosuppressive agents, anti-tumor necrosis factor alpha (anti-TNF-α) and anti-integrin antibodies, focus on the symptoms but not on the cause of the disease. Adherent-invasiveEscherichia coli(AIEC) bacteria abnormally colonize the ileal mucosa of CD patients via the interaction of the mannose-specific adhesin FimH of type 1 pili with CEACAM6 mannosylated proteins expressed on the epithelial cell surface. Thus, we decided to develop an antiadhesive strategy based on synthetic FimH antagonists specifically targeting AIEC bacteria that would decrease intestinal inflammation. Heptylmannoside (HM)-based glycocompounds strongly inhibit AIEC adhesion to intestinal epithelial cellsin vitro. The antiadhesive effect of two of these compounds of relatively simple chemical structure was also observedin vivoin AIEC-infected CEACAM6-expressing mice and was associated with a reduction in the signs of colitis. These results suggest a new therapeutic approach for CD patients colonized by AIEC bacteria, based on the development of synthetic FimH antagonists.

scholarly journals HtrA Stress Protein Is Involved in Intramacrophagic Replication of Adherent and Invasive Escherichia coli Strain LF82 Isolated from a Patient with Crohn's Disease

2005 ◽  
Vol 73 (2) ◽  
pp. 712-721 ◽  
Author(s):  
Marie-Agnès Bringer ◽  
Nicolas Barnich ◽  
Anne-Lise Glasser ◽  
Olivier Bardot ◽  
Arlette Darfeuille-Michaud
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Stress Protein ◽  
Gene Promoter ◽  
Coli Strain ◽  
Gene Encoding ◽  
Reduced Rate ◽  
K 12

ABSTRACT Adherent and invasive Escherichia coli (AIEC) bacteria isolated from Crohn's disease patients are able to greatly replicate within macrophages without escaping from the phagosome and without inducing macrophage death. In the present study, evidence is provided that in AIEC strain LF82 the htrA gene encoding the stress protein HtrA is essential for intracellular replication within J774-A1 macrophages. Deletion of the htrA gene in strain LF82 induced increased sensitivity of the isogenic mutant to oxidative stress caused by hydrogen peroxide and a reduced rate of growth in an acid and nutrient-poor medium partly reproducing the microenvironment of the phagosome. In vitro experiments using an LF82 htrA gene promoter fusion with the lacZ gene revealed a 38-fold activation of the promoter in AIEC LF82 intramacrophagic bacteria. The CpxRA two-component signaling pathway was not involved in this activation. In addition, the activation of the LF82 htrA gene promoter was not observed in the nonpathogenic E. coli K-12 intramacrophagic bacteria, indicating that the AIEC LF82 genetic background is crucial for induction of htrA gene transcription during phagocytosis.

scholarly journals Analysis of the σERegulon in Crohn's Disease-Associated Escherichia coli Revealed Involvement of thewaaWVLOperon in Biofilm Formation

2015 ◽  
Vol 197 (8) ◽  
pp. 1451-1465 ◽  
Author(s):  
Benoit Chassaing ◽  
Estelle Garénaux ◽  
Jessica Carriere ◽  
Nathalie Rolhion ◽  
Yann Guérardel ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Mucosa ◽  
Biofilm Formation ◽  
Intestinal Epithelial ◽  
Content Type ◽  
E Coli ◽  
Gut Mucosa ◽  
Pathway Inhibition

ABSTRACTIleal lesions of patients with Crohn's disease are colonized by adherent-invasiveEscherichia coli(AIEC), which is able to adhere to and to invade intestinal epithelial cells (IEC), to replicate within macrophages, and to form biofilms on the surface of the intestinal mucosa. Previous analyses indicated the involvement of the σEpathway in AIEC-IEC interaction, as well as in biofilm formation, with σEpathway inhibition leading to an impaired ability of AIEC to colonize the intestinal mucosa and to form biofilms. The aim of this study was to characterize the σEregulon of AIEC strain LF82 in order to identify members involved in AIEC phenotypes. Using comparativein silicoanalysis of the σEregulon, we identified thewaaWVLoperon as a new member of the σEregulon in reference AIEC strain LF82. We determined that thewaaWVLoperon is involved in AIEC lipopolysaccharide structure and composition, and thewaaWVLoperon was found to be essential for AIEC strains to produce biofilm and to colonize the intestinal mucosa.IMPORTANCEAn increased prevalence of adherent-invasiveEscherichia coli(AIEC) bacteria was previously observed in the intestinal mucosa of Crohn's disease (CD) patients, and clinical observations revealed bacterial biofilms associated with the mucosa of CD patients. Here, analysis of the σEregulon in AIEC and commensalE. coliidentified 12 genes controlled by σEonly in AIEC. Among them, WaaWVL factors were found to play an essential role in biofilm formation and mucosal colonization by AIEC. In addition to identifying molecular tools that revealed a pathogenic population ofE. colicolonizing the mucosa of CD patients, these results indicate that targeting thewaaWVLoperon could be a potent therapeutic strategy to interfere with the ability of AIEC to form biofilms and to colonize the gut mucosa.

P789 Bacteriological profile of material collected from perianal lesions from patients with Crohn’s disease in the tertiary IBD centre in southern Poland

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S622-S622
Author(s):  
R Filip ◽  
J Gruszecka
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bacterial Species ◽  
Antibiotic Sensitivity ◽  
Beta Lactam ◽  
Anal Abscess ◽  
Extended Spectrum Beta Lactamase

Abstract Background Both anal abscesses and fistulas are potential complications in the course of Crohn’s disease. Chronic immunosuppression, loose stools and poor wound healing in this population pose a challenge to the treatment of perianal diseases. The purpose of our hospital research was to determine the dominant bacterial species found in perianal abscesses and fistula discharge, resulting in anal abscess and/or fistula outflow in patients with Crohn’s disease hospitalised in a tertiary IBD centre in Poland. Methods The results of tests of patients admitted and subsequently conservatively treated or treated for anal fistula or abscess in the period from January 1, 2017 to June 30, 2019 were evaluated. Information obtained from medical records included clinical information, results of laboratory tests and results of swab cultures of perianal lesions for culturing and antibiotic sensitivity of microorganisms isolated. Material was collected from patients in accordance with applicable procedures. Results In the analysed period, a total of 306 swabs from perianal lesions from 44 patients with the diagnosis of Crohn’s Disease were collected, of which microbial growth was observed in 38 patients. Escherichia coli (45.5%, p < 0.001) was the most frequently isolated pathogen, Staphylococcus aureus was the second most common pathogen (15.9%, p < 0.001). In vitro sensitivity tests showed that Escherichia coli (ESBL-extended-spectrum-beta-lactamase producing strain with a broader substrate spectrum) was found in 4 samples, Staphylococcus aureus (MRSA- strain resistant to all beta-lactam antibiotics: penicillins with inhibitors, cephalosporins, monobactams, carbapenems except for ceftaroline). The analysis of the results obtained did not show seasonal variability in the number of positive microbiological tests found on cultures of perianal lesions. Conclusion A retrospective analysis of microbiological results of anal abscesses and fistula outflow was performed in patients with Crohn’s Disease with perianal changesi. Escherichia coli was the predominant pathogen isolated. The second most common organism was Staphylococcus, isolated from 9 patients. Staphylococci were not found in samples from other patients with IBD. The evaluation of the obtained results shows that positive results of cultures of swabs from lesions in the anal area were found more often in samples taken from men (25 samples–65.8%) than from women (13 samples–34.2%).

scholarly journals A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent InvasiveEscherichia coli

2019 ◽  
Author(s):  
Robert Cogger-Ward ◽  
Adam Collins ◽  
Denise McLean ◽  
Jacob Dehinsilu ◽  
Alan Huett
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Caenorhabditis Elegans ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Biofilm Formation ◽  
Chronic Inflammatory Bowel Disease ◽  
Infection Model ◽  
Flagellar Motility ◽  
C Elegans

AbstractAdherent InvasiveEscherichia coli(AIEC) is a non-diarrhoeagenic intestinalE. colipathotype associated with Crohn’s Disease. AIEC pathogenesis is characterised by biofilm formation, adhesion to and invasion of intestinal epithelial cells, and intracellular replication within epithelial cells and macrophages. Here, we identify and characterise a protein in the prototypical AIEC strain LF82 which is required for efficient biofilm formation and dispersal – LF82_p314. LF82 ΔLF82_314have defective swimming and swarming motility, indicating LF82_p314 is important for flagellar-mediated motility, and thus surface colonisation and biofilm dispersal. Flagellar morphology and chemotaxis in liquid appear unaffected by deletion ofLF82_314, suggesting LF82_p314 does not elicit an effect on flagella biogenesis or environmental sensing. Flagellar motility has been implicated in AIEC virulence, therefore we assessed the role of LF82_p314 in host colonisation using aCaenorhabditis elegansmodel. We found that LF82 ΔLF82_314have an impaired ability to colonise theC. eleganscompared to wild-type LF82. Phylogenetic analysis showed thatLF82_314is conserved in several major enterobacterial pathogens, and suggests the gene may have been acquired horizontally in several genera. Our data suggests LF82_p314 may be a novel component in the flagellar motility pathway and is a novel determinant of AIEC colonisation. Our findings have potential implications not only for the pathogenesis of Crohn’s Disease, but also for the course of infection in several major bacterial pathogens. We propose a new designation forLF82_314,biofilmcoupled tomotilityA, orbcmA.Author summaryAdherent InvasiveEscherichia coli(AIEC) are a group of bacteria implicated in the pathogenesis of Crohn’s Disease, a chronic inflammatory bowel disease with no cure. Critical to the process of many bacterial infections is the ability of bacteria to swim towards and colonise the host surface using specialised, propeller-like appendages called flagella. In this paper, we describe a novel protein – LF82_p314 (BcmA) – which is required for efficient flagella-mediated motility and surface colonisation in AIEC. Using a nematode worm (Caenorhabditis elegans) infection model, we show that LF82_p314 enables effective colonisation of theC. elegansgut, suggesting a role for the protein during human infection. These findings indicate BcmA is significant for initial colonisation of the human gut by AIEC, and therefore the onset of Crohn’s Disease.

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