The HtrA-like protease CD3284 modulates virulence of clostridium difficile

Bakker, D., Buckley, A.M., de Jong, A., van Winden, V.J.C., Verhoeks, J.P.A., Kuipers, O.P., Douce, G.R. , Kuijper, E.J., Smits, W.K. and Corver, J. (2014) The HtrA-like protease CD3284 modulates virulence of clostridium difficile. Infection and Immunity, 82(10), pp. 4222-4232. (doi: 10.1128/IAI.02336-14) (PMID:25047848) (PMCID:PMC4187886)

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Abstract

In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis. Besides the two main virulence factors toxin A and toxin B, other virulence factors are likely to play a role in the pathogenesis of the disease. In other Gram-positive and Gram-negative pathogenic bacteria, conserved high-temperature requirement A (HtrA)-like proteases have been shown to have a role in protein homeostasis and quality control. This affects the functionality of virulence factors and the resistance of bacteria to (host-induced) environmental stresses. We found that the C. difficile 630 genome encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its role in vivo and in vitro through the creation of an isogenic ClosTron-based htrA mutant of C. difficile strain 630Δerm (wild type). In contrast to the attenuated phenotype seen with htrA deletion in other pathogens, this mutant showed enhanced virulence in the Golden Syrian hamster model of acute C. difficile infection. Microarray data analysis showed a pleiotropic effect of htrA on the transcriptome of C. difficile, including upregulation of the toxin A gene. In addition, the htrA mutant showed reduced spore formation and adherence to colonic cells. Together, our data show that htrA can modulate virulence in C. difficile.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Douce, Dr Gillian and Buckley, Dr Anthony
Authors: Bakker, D., Buckley, A.M., de Jong, A., van Winden, V.J.C., Verhoeks, J.P.A., Kuipers, O.P., Douce, G.R., Kuijper, E.J., Smits, W.K., and Corver, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
492111Genetic and phenotypic characterisation of emerging virulent Clostridium difficileGillian DouceWellcome Trust (WELLCOME)086418/B/08/ZIII - BACTERIOLOGY