Salmonella infection is a major public health problem with Salmonella spp. causing more than one billion new human infections each year that lead to more than three million deaths. The problem is greatly exacerbated by the emergence of multi-drug resistant strains. The public health threat of Salmonella is heightened by the fact that this NIAID Category B pathogen could be used as a weapon of bioterrorism, given the ease with which it can be propagated and its environmental stability. In fact, Salmonella is one of only a handful of pathogens that has been successfully used as a weapon. We have observed that Salmonella secretes the protein SrfH into infected cells to activate their motility by manipulating the host protein TRIP6, to accelerate the systemic spread of infection. At later stages of infection, SrfH can bind the host protein IQGAP1 to inhibit productive, infected macrophage motility, perhaps to avoid interactions with immune system cells. The objectives of this work are to: understand mechanistically how SrfH subverts the host protein TRIP6 to accelerate productive, infected macrophage motility early in infection understand the impact of the separable abilities of SrfH to promote and inhibit productive, infected macrophage motility on Salmonella virulence in mouse models of infection disentangle spatial and temporal regulation models to account for the ability of SrfH to both promote and repress productive, infected macrophage motility at different times during infection
Salmonella infection is a major public health problem with Salmonella spp. causing more than one billion new human infections each year that lead to more than three million deaths1. The problem is greatly exacerbated by the emergence of multi-drug resistant strains2. It is the goal of this work to understand how, when, where and why pathogens move within their hosts. The answers to these questions may directly affect human health.
| Thornbrough, Joshua M; Worley, Micah J (2012) A naturally occurring single nucleotide polymorphism in the Salmonella SPI-2 type III effector srfH/sseI controls early extraintestinal dissemination. PLoS One 7:e45245 |
