Unravelling the dynamic interactions between protective Esherichia coli and pathogenic Salmonella

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BACKGROUND: Bacterial infections are a major cause of morbidity and mortality in humans and farm-animals and falls within the BBSRC priority of "Bioscience for sustainable agriculture and food". The probiotic Escherichia coli strain Nissle 1917 (EcN) provides protection against food-borne pathogens and infectious diarrheal diseases by mechanisms not yet fully characterized, and falls within the BBSRC priority of "Bioscience for an integrated understanding of health". HYPOTHESIS: The probiotic interactions between Escherichia coli Nissle and Salmonella involve intra-bacterial cell-to-cell contact, prophage encoded factors, and biochemical signalling. RESEARCH PLAN: This studentship aims to define the interactions between the probiotic EcN and the foodborne pathogen Salmonella Enteritidis (Salmonella), identifying the molecular mechanisms of EcN mediating reduced virulence and pathogenicity of Salmonella. We have developed gastrointestinal tract-relevant, in vitro co-culture conditions, and generated important preliminary data. In the presence of EcN, the expression of major Salmonella virulence factors, e.g. the Salmonella pathogenicity island (SPI-1) type 3 secretion system (T3SS) and flagella, is drastically reduced, and the reductions are dependent on a large, diffusible, heat-resistant factor generated by EcN. The EcN genome also harbors 5-6 genomic regions bioinformatically identified as cryptic prophages that are not present in other E.coli strains and are highly expressed in co-culture with pathogenic E.coli . We will investigate how all these factors contribute to the probiotic nature of EcN using a combination of refined culturing, biochemical characterisation, transposon mutagenesis, transcriptomics, and in vivo culture.