Bacterial pathogens often secrete proteins into their environment to institute infection of eukaryotic host cells. Common virulence-associated protein secretion machineries are the well studied type III and IV systems that facilitate proteins to associate with and translocate into eukaryotic cells. The principal bacterial food-borne pathogen Campylobacter jejuni and related species lack these systems but seem to have evolved alternative protein secretion strategies. So far, a few Campylobacter virulence-associated proteins have been identified. Most of these proteins appear to be secreted by the flagellar export system, some in response to host factors. The mechanism of this novel host-induced protein secretion pathway and the function of the secreted proteins, are unknown. The goal of this project is to dissect the mechanism(s) and function in cellular infection of Campylobacter protein secretion. More specifically, it is aimed: 1) to identify Campylobacter proteins and their secretion routes using a subproteome approach; 2) to decipher the regulation of host-induced bacterial protein secretion and their role in cellular infection using defined mutants, tagged recombinant proteins, and multiphoton confocal microscopy, and 3) to unravel the function of selected secreted proteins in host cell infection. This work is expected to expand our knowledge of host-pathogen interactions and to lead to the discovery of the control and function in cellular infection of bacterial protein secretion systems distinct from the classical type III and IV secretion machineries. The results may thus provide novel targets for vaccine and drug development against bacterial pathogens.
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