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BEGIN:VEVENT
DTSTAMP:20260513T125339Z
DTSTART;VALUE=DATE-TIME:20191126T120000
DTEND;VALUE=DATE-TIME:20191126T130000
SUMMARY:SLS/WMS Micro Seminar: The complicated world of Clostridium diffi
 cile\, Dr Lisa Dawson\, London School of Hygiene and Tropical Medicine
TZID:Europe/London
UID:20191126-8a17841b6dde7e75016e16f49e2a772c@warwick.ac.uk
CREATED:20191125T151519Z
DESCRIPTION:Abstract: Clostridium difficile is the major cause of antibio
 tic-associated diarrhoea world-wide. Disruption of the commensal microbi
 ota\, such as through use of broad-spectrum antibiotics\, is key for col
 onisation by C. difficile and development of C. difficile disease (CDI).
  Furthermore\, failure of the gut microbiota to recover diversity and re
 -establish a healthy microbiota\, results in recurrence of infection. Af
 ter an initial recurrent episode\, patients are more likely to relapse m
 ultiple times. Understanding the mechanisms behind colonisation\, relaps
 e and virulence in C. difficile will provide an insight into development
  of novel treatments for C. difficile. Virulence factor of C. difficile\
 , which contribute to disease\, colonisation and transmission include \;
  spores\, flagella\, cell surface proteins\, biofilm formation and p-cre
 sol production. An unusual characteristic of C. difficile among gut bact
 eria is its ability to produce the bacteriostatic compound para-cresol t
 hrough fermentation of tyrosine\, via an intermediate para-hydroxyphenyl
  acetate (p-HPA). Here\, we investigate the interaction of C. difficile 
 with other commensal microbiota and the effect that p-cresol production 
 by C. difficile has on their growth and microbial diversity. Using a gen
 e inactivation mutant (hpdC::CT) of the decarboxylase responsible for th
 e conversion of p-HPA to p-cresol\, we demonstrate that p-cresol product
 ion provides a competitive advantage for C. difficile over commensal gut
  bacteria\; E. coli\, K. oxytoca and B. thetaiotaomicron. Metabolic prof
 iling highlights the importance of acetate\, butyrate\, p-cresol and p-H
 PA in driving separation of wild-type C. difficile from a p-cresol mutan
 t. Removing the ability to convert p-HPA to p-cresol leads to a fitness 
 defect in a mouse relapse model of C. difficile infection. These mice ha
 ve a distinctly altered gut microbiota composition\, alongside altered f
 aecal metabolite profiles. We demonstrate that Gammaproteobacteria are s
 usceptible to exogenous p-cresol in-vitro and that there is a clear divi
 de between bacterial Phyla and their susceptibility to p¬¬-cresol. The G
 ram-negative species were relatively sensitive to p-cresol\, whereas Gra
 m-positive species were more tolerant. This study demonstrates that prod
 uction of p-cresol by C. difficile has an effect on relapse of CDI in a 
 mouse model of infection\, as well as the viability of Gram-negative com
 mensal intestinal bacteria and metabolite production\, suggesting that p
 -cresol production directly or indirectly contributes to C. difficile pa
 thogenesis.
LOCATION:BSR1\, School of Life Sciences
CATEGORIES:BiomedicalSciences,DivisionalSeminars,Joint WMS/SLS Micro
LAST-MODIFIED:20191125T151519Z
ORGANIZER;CN=Jas Bains:
END:VEVENT
END:VCALENDAR