Relatively little is known about Salmonella Virchow as a pathogen. Its prevalence varies from country to country, however it is constantly associated with invasive disease, particularly in children and the immuno-compromised. The main sources of S. Virchow are humans and poultry. The aims of this study were to determine the genetic relatedness of S. Virchow isolates from difference sources in England, to characterise its infection biology using in vitro and in vivo based models, to establish the immune response produced by poultry in response to infection with the serovar and to begin to determine the level of protection and cross-protection that could be achieved against the serovar and S. Typhimurium. The genetic relatedness of the S. Virchow isolates was determined using molecular typing techniques including MLST and PFGE. The isolates were screened for the presence of 12 virulence genes that have been associated with adhesion, invasion and persistence. Human and avian cell lines and in vivo poultry infection experiments were used to characterise S. Virchow’s invasiveness, persistence and ability to elicit an immune response, compared to a well characterised S. Typhimurium isolate. Immune responses were evaluated by immunohistochemistry, RT-PCR and ELISA, to establish aspects of the innate, cellular and humoral response, as well as cytokine and chemokine expression. An in vivo poultry infection experiment was performed to gain an indication of the level of protection and cross-protection offered by primary infection with S. Virchow against secondary infection. Bacteriology, ELISA and western blot methods were used analyse this. Overall, S. Virchow appears to be a relatively clonal serovar, regardless of the source and the results indicate this is widespread and not solely in the UK. All of the isolates possessed the 12 virulence genes, which could contribute to its virulence in some hosts. S. Virchow was particularly persistent and inflammatory in the human Caco2 cells, which is consistent with the increased virulence previously reported in humans. The in vitro HD11 assay and the in vivo poultry infection experiments were consistent in showing S. Virchow colonises the chicken intestine to high levels, causes transient systemic infection and stimulates a moderate inflammatory response, very similar to S. Typhimurium infection. S. Virchow infection stimulated all aspects of the chicken immune system, characteristic of a broad-range serovar. Initial results from the in vivo protection experiment showed primary infection with S. Virchow does offer some protection against systemic invasion, although adequate protection against caecal colonisation was not found. However, 2 proteins were identified that strongly reacted and cross-reacted with sera from infected chickens, providing optimism that a vaccine to protect against S. Virchow colonisation could be developed with further research.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:579274 |
| Date | January 2012 |
| Creators | Salisbury, Anne |
| Contributors | Wigley, Paul; Carter, Stuart |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/9133/ |
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