Characterization of effector proteins translocated via the SPI1 type III secretion system of Salmonella typhimurium.

Salmonella spp. employ a conserved type III secretion system encoded within the pathogenicity island 1 (SPI1; centisome 63) to translocate effector proteins into the host cytosol. The translocated effector proteins trigger diverse responses including bacterial internalization. In a mutation analysis we have defined the set of effector proteins mediating tissue culture cell invasion. This set includes sopE2 (centisome 40-42), sopB (SPI5, centisome 20) and in the case of S. typhimurium SL1344 also the phage-encoded effector sopE (SopEphi, centisome 59-60). A triple mutant SL1344 derivative deficient of SopE, SopE2 and SopB was more than 100-fold attenuated in tissue culture cell invasion. Phylogenetic analyses indicate that the last common ancestor of all contemporary Salmonella lineages already harbored all genes necessary for host cell invasion, namely the SPI1 type III secretion system, sopE2 and sopB. SopE, which is 70% identical to sopE2 is only present in some Salmonella strains and emerged later well after the divergence of the contemporary Salmonella lineages. Interestingly, S. typhimurium strains that harbor sopE are associated with epidemics, arguing that sopE is one of the factors determining the "fitness" of a strain. We found that SopE can specifically activate a different set of host cellular RhoGTPases than SopE2. This allows the bacteria to fine tune host cellular responses very precisely and may offer an explanation for the improved epidemic fitness of sopE-positive S. typhimurium strains.

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