Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse

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Lister, Michelle M. (2018) Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse. PhD thesis, University of Nottingham.

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Abstract

Clostridium difficile is the leading cause of health care associated diarrhoea and remains a burden for the NHS. Disease symptoms can range from mild diarrhoea through to fulminant pseudomembranous colitis, resulting in mortality for some patients. Recurrence is a major problem and estimates are that 20% of all patients with disease will either relapse (with the same strain) or have a re-infection (with a different strain).

Arguably, the main virulence factors are toxins A (TcdA) and toxin B (TcdB) which cause disease symptoms. The genes encoding TcdA and TcdB are located within the pathogenicity locus (PaLoc) along with three accessory genes; tcdR, tcdE and tcdC. The regulatory network has been studied but we aimed to add to this knowledge by using two under investigated strains R20291 a so-called hypervirulent strain and VPI 10463 a strain known to produce higher levels of toxin.

Two different methods of investigation were employed during this study to improve our understanding of both the regulation of TcdA / TcdB but also the genetic mechanisms behind clinical relapse. These methods were; using forward and reverse genetic analysis to assess phenotypic differences and using bioinformatics to identify genes and / or single nucleotide variants (SNP) that may play a role.

Using a combination these methods we have identified potential regulators of toxin production in both strains. We have also identified unique genes and SNPs that might provide a fitness benefit to strains of C. difficile that were isolated from patients who had suffered relapse episodes.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Kuehne, Sarah A.
Minton, Nigel P.
Cockayne, A.
Subjects: Q Science > QH Natural history. Biology > QH426 Genetics
Q Science > QR Microbiology > QR 75 Bacteria. Cyanobacteria
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 53216
Depositing User: Lister, Michelle
Date Deposited: 13 Dec 2018 04:40
Last Modified: 13 Dec 2020 04:30
URI: https://eprints.nottingham.ac.uk/id/eprint/53216

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