Molecular basis of virulence of Salmonella enterica and avian pathogenic Escherichia coli in poultry

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Salmonella enterica is an animal and zoonotic pathogen of worldwide importance. Infections in poultry may present in a variety of ways, from asymptomatic colonisation of the intestines and oviduct to typhoid fever depending on serovar- and host-specific factors. The molecular basis of intestinal and reproductive tract colonisation by Salmonella, as well as the differential virulence of serovars, is ill-defined. Avian pathogenic E. coli (APEC) also pose a substantial threat to food security via induction of colibacillosis, a severe and recalcitrant disease associated with bacterial translocation from mucosal surfaces to the blood and distal organs. Ongoing BBSRC-funded research aims to identify S. Typhimurium and APEC O78 factors required for colonisation and penetration of mucosal surfaces by screening random transposon mutants (1255, 1291). In addition, we are deriving the complete genome sequence of APEC O78 in collaboration with the Sanger Institute and pyrosequencing the genomes of S. enterica strains representing several serovars of well-defined virulence at IAH. Hundreds of candidate virulence factors have been identified by screening random mutants, however further studies are required to confirm the role of selected loci and eliminate the possibility that phenotypes are a consequence of polar or second-site defects. In addition, in silico analysis of the genomes of S. enterica strains is identifying loci that may be involved in the differential virulence and host- or tissue-tropism of serovars. We will define the role of candidate virulence factors of Salmonella and APEC by construction of defined mutants (using suicide replicons or recombinase-based methods) and analysis in animal and cell-based models alongside parent and repaired or trans-complemented strains. The conservation of virulence factors in natural populations and host adaptive immune response to selected factors will be quantified to aid the rational design of intervention strategies.

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