Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse
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 t...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2018
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| Online Access: | https://eprints.nottingham.ac.uk/53216/ |
| _version_ | 1848798903233675264 |
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| author | Lister, Michelle M. |
| author_facet | Lister, Michelle M. |
| author_sort | Lister, Michelle M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:27:10Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-53216 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:27:10Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-532162025-02-28T12:06:38Z https://eprints.nottingham.ac.uk/53216/ Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse Lister, Michelle M. 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. 2018-12-13 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/53216/1/Lister_Genetics%20of%20Clostridium%20difficile%20toxin%20and%20recurrence.pdf Lister, Michelle M. (2018) Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse. PhD thesis, University of Nottingham. |
| spellingShingle | Lister, Michelle M. Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title | Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title_full | Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title_fullStr | Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title_full_unstemmed | Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title_short | Understanding the genetic mechanisms of Clostridium difficile toxin regulation and clinical relapse |
| title_sort | understanding the genetic mechanisms of clostridium difficile toxin regulation and clinical relapse |
| url | https://eprints.nottingham.ac.uk/53216/ |