Investigating Pathogenesis and Virulence of the Human Pathogen, Vibrio vulnificus.
Church, Selina Rebecca
Thesis or dissertation
University of Exeter
V. vulnificus is a Gram negative opportunistic pathogen that is ubiquitous in the marine environment. Of the three main biotypes, biotype 1 is most commonly associated with human infection and is the causative agent of septicaemia, gastroenteritis and wound infection. In the United States V. vulnificus is the leading cause of seafood related deaths and is commonly associated with ingestion of raw or undercooked oysters. However, despite the abundant prevalence of this bacterium in the environment, the number of severe human infections is low. This has led to the hypothesis that not all strains of this pathogen are equal in virulence, with some strains better adapted to causing human disease than others. Therefore the current study tested a panel of 10 V. vulnificus strains in several phenotypic experiments that assayed the strains for known virulence factors, with the aim of identifying a marker for strains hazardous to human health. However, not one assay correlated with either virulence potential of the strains, as determined by an in vivo mouse model of virulence, or source of isolation. As the study hypothesised that the varying virulence potentials displayed by the strains may be due to genetic differences, whole genome sequencing (WGS) was performed. Bioinformatic comparison of the strains demonstrated many genetic differences between the strains. However, in unison with the WGS comparison, WGS gene annotation was also performed. This identified the presence of two previously undescribed type 6 secretion systems (T6SS). Therefore the current study continued investigation into the T6SSs. The two T6SSs identified were termed T6SS1 and T6SS2. T6SS2 was found in all sequenced isolates, whereas T6SS1 was only present in a sub-set of strains. As T6SS1 shared synteny with the previously described T6SS in V. cholerae, T6SS1 was chosen for further investigation. During this study T6SS1 was shown to be functional and displayed thermoregulation. Further investigation into T6SS1 by construction and characterising of a T6SS1 mutant, demonstrated that T6SS1 contained anti-prokaryotic properties.
PhD in Biological Sciences