Show simple item record

dc.contributor.authorPassmore, Ian J
dc.contributor.authorLetertre, Marine P M
dc.contributor.authorPreston, Mark D
dc.contributor.authorBianconi, Irene
dc.contributor.authorHarrison, Mark A
dc.contributor.authorNasher, Fauzy
dc.contributor.authorKaur, Harparkash
dc.contributor.authorHong, Huynh A
dc.contributor.authorBaines, Simon D
dc.contributor.authorCutting, Simon M
dc.contributor.authorSwann, Jonathan R
dc.contributor.authorWren, Brendan W
dc.contributor.authorDawson, Lisa F
dc.date.accessioned2018-10-17T15:04:42Z
dc.date.available2018-10-17T15:04:42Z
dc.date.issued2018-09-12
dc.identifier.citationPassmore , I J , Letertre , M P M , Preston , M D , Bianconi , I , Harrison , M A , Nasher , F , Kaur , H , Hong , H A , Baines , S D , Cutting , S M , Swann , J R , Wren , B W & Dawson , L F 2018 , ' Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria ' , PLoS Pathogens , vol. 14 , no. 9 , e1007191 , pp. e1007191 . https://doi.org/10.1371/journal.ppat.1007191
dc.identifier.issn1553-7366
dc.identifier.otherPURE: 15345322
dc.identifier.otherPURE UUID: ec92d88d-3ac0-441b-9a08-1856b7c1fe29
dc.identifier.otherPubMed: 30208103
dc.identifier.otherScopus: 85054557435
dc.identifier.urihttp://hdl.handle.net/2299/20720
dc.description.abstractClostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.en
dc.language.isoeng
dc.relation.ispartofPLoS Pathogens
dc.rightsOpen
dc.subjectParasitology
dc.subjectMicrobiology
dc.subjectImmunology
dc.subjectMolecular Biology
dc.subjectGenetics
dc.subjectVirology
dc.titlePara-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteriaen
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85054557435&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2018-09-12
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1371/journal.ppat.1007191
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record