Characterizing the role of the spectrin cytoskeleton during adherent and invasive bacterial pathogenesis

The enteric pathogens, enteropathogenic Escherichia coli (EPEC), Salmonella Typhimurium and Listeria monocytogenes cause millions of infections worldwide each year. A shared host cell target of these microbes is the cytoskeleton, which is reorganized as part of the infectious process. Because the hijacking of the cytoskeleton is a pre-requisite for disease, I hypothesized that the spectrin cytoskeleton would be targeted by these pathogens. I investigated three major components of the spectrin cytoskeleton: spectrin, adducin and protein 4.1. Using immunolocalization techniques, I identified spectrin cytoskeletal components recruited to EPEC pedestals, S. Typhimurium membrane invasion ruffles and Salmonella containing vacuoles (SCVs), as well as L. monocytogenes actin phagocytic cups and sites of initial comet tail formation. When any of the spectrin cytoskeletal proteins were knocked down, pathogenesis of each organism was severely attenuated. These findings reveal a novel host cell cytoskeletal network that is crucial for both adherent and invasive bacterial disease.