Characterisation of a putative quorum sensing system in Colstridium difficile

Patel, Manisha R. (2011) Characterisation of a putative quorum sensing system in Colstridium difficile. PhD thesis, University of Nottingham.

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Abstract

Clostridium difficile is the major cause of health-care associated infections. However the factors that participate in C. difficile infection and the processes that regulate their expression remains poorly understood.

In Staphylococcus aureus, quorum sensing (QS) plays a central role in the regulation of virulence factors. The QS system of S. aureus is encoded by the accessory gene regulator (agr) locus and comprises of four genes. The pre-peptide (AgrD) is processed by AgrB and the mature auto-inducing peptide (AIP) is released into the medium. Free AIP binds to the histidine-sensor kinase AgrC, causing it to autophosphorylate. In turn, AgrC phosphorylates the response regulator AgrA, triggering an intracellular signal-transduction cascade which results in altered expression of several target genes.

Homologues of genes involved in QS have been identified in the genome sequence of C. difficile 630, a virulent multidrug resistant strain. These homologues have also been identified in C. difficile R20291, a ribotype 027 epidemic strain, which has been characterised to produce increased quantities of Toxin A and Toxin B. C. difficile R20291 has two agr loci, whereas C. difficile 630 only has one agr locus. The first agr locus present in both strains contains agrBD homologues, although there are no apparent agrAlagrC homologues. However, the second agr locus in C. difficile R20291 contains homologues of all four agr genes. Insertional inactivation of the QS homologues were made in the two C. difficile strains and the effects on virulence assessed. Cytotoxicity assays indicated that there is a substantial reduction in toxin B production in C. difficile R20291 strains deficient in the second agr system compared to the wild-type strain. Sporulation assays revealed that the onset of sporulation in the agr mutants vary greatly in comparison to the parental strain. The work presented in this study suggests that the agr system may be involved in toxin production and sporulation in C. difficile.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Chan, W.C.
Minton, N.P.
Keywords: Quorum sensing, Virulence factors, Accessory gene regulator
Subjects: QS-QZ Preclinical sciences (NLM Classification) > QW Microbiology. Immunology > QW1 Microbiology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Molecular Medical Sciences
Item ID: 13570
Depositing User: EP, Services
Date Deposited: 04 Sep 2013 07:20
Last Modified: 14 Sep 2016 22:37
URI: http://eprints.nottingham.ac.uk/id/eprint/13570

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