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Cambridge Immunology Network



Supervisors: Professor Gordon Dougan, Professor Ken Smith and Rob Kingsley

Hypervariable loci in a clonal pathogen: Characterisation of a two-component regulatory system in Salmonella enterica
Salmonella Typhi is the causative agent of typhoid fever, a bloodstream infection, which infects 27 million people a year worldwide and results in more than 200,000 deaths per year. The bacteria have adapted and many are now resistant to common antibiotics making it harder to eradicate this disease. Previous studies identified hypervariable genes in S. Typhi that may be involved in recent adaptation. These include a locus encoding a putative two-component regulator family protein for which the function is currently not known. These regulatory systems operate by exploiting a signal-sensing domain on a histidine protein kinase that autophosphorylates and then transfer the phosphoryl group to a cognate response regulator that mediates the activity of gene expression, in response to particular environmental signals. This project will explore the role by which natural variants of these genes influence the biology of S. Typhi, impacting on phenotypes such as virulence, metabolism and antibiotic resistance. The significance of this work is that through understanding how these genes operate we can develop new strategies to combat this ever-increasing threat to public health.

Dr Vanessa  Wong
Not available for consultancy


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