The role of Clostridium perfringens in intestinal diseases

Kiu Kwong Ong, Raymond (2018) The role of Clostridium perfringens in intestinal diseases. Doctoral thesis, University of East Anglia.

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Clostridium perfringens, a spore-forming bacterium that produces >20 toxins, is known to cause both human and animal intestinal diseases including; foodborne diarrhoea, preterm necrotising enterocolitis (NEC) and necrotic enteritis (NE) in chickens. Currently, there is very limited information on genomic virulence determinants, and the phylogenic and epidemiology landscape of this enteric pathogen, thus in this thesis I sought to comprehensively explore intestinal-associated C. perfringens strains using both genomic and phenotypic methodologies.
Whole Genome Sequencing (WGS) and bioinformatic approaches was used to examine a novel collection of C. perfringens isolates and publically available genomes (n=552, including 109 public genomes) from a diverse range of hosts and disease states including; NEC-associated preterm infants, foodborne diarrhoea patients, NEassociated broilers, and healthy humans and animals. These genomes were analysed in combination or as discreet disease subsets to determine infection-linked virulence features, genomic epidemiology and hyper-virulent genotypes, and indicated a highly diverse pangenome (7.4% core genome), toxin-specific and novel virulence factors, widespread distribution of conjugative plasmids, long-term persistence, and interregional transmission events during disease outbreaks. This work represents the largest WGS-based phylogenetic and comparative genomics on C. perfringens to date.
Furthermore, a sub-set of C. perfringens isolates were characterised phenotypically using microbiological assays to determine hyper-virulent phenotypes, which linked to genomic analysis. These hyper-virulent strains were then used to establish a novel C. perfringens oral-challenge mouse model. This enteric infection model will allow further mechanistic work in understanding the role of C. perfringens in relevant intestinal diseases and may be used to facilitate therapy or vaccine development.
Overall, this multidisciplinary work provides important novel insights into the intestinal pathogen C. perfringens at both a genomic and phenotypic level and provides a platform for subsequent translational studies into efforts to reduce C. perfringens-associated disease burden in both humans and animals.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Jackie Webb
Date Deposited: 09 Apr 2019 11:35
Last Modified: 30 Apr 2021 00:38


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