The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice

Abstract

SummarySalmonella resides within host cells in a vacuole that it modifies through the action of virulence proteins called effectors. Here we examined the role of two related effectors, SopD and SopD2, in Salmonella pathogenesis. Salmonella enterica serovar Typhimurium ( S. Typhimurium) mutants lacking either sopD or sopD2 were attenuated for replication in the spleens of infected mice when competed against wild-type bacteria in mixed infection experiments. A double mutant lacking both effector genes did not display an additive attenuation of virulence in these experiments. The double mutant also competed equally with both of the single mutants. Deletion of either effector impaired bacterial replication in mouse macrophages but not human epithelial cells. Deletion of sopD2 impaired Salmonella 's ability to form tubular membrane filaments [ Salmonella -induced filaments (Sifs)] in infected cells; the number of Sifs decreased, whereas the number of pseudo-Sifs (thought to be a precursor of Sifs) was increased. Transfection of HeLa cells with the effector SifA induced the formation of Sif-like tubules and these were observed in greater size and number after co-transfection of SifA with SopD2. In infected cells, SifA and SopD2 were localized both to Sifs and to pseudo-Sifs. In contrast, deletion of sopD had no effect on Sif formation. Our results indicate that both SopD and SopD2 contribute to virulence in mice and suggest a functional relationship between these two proteins during systemic infection of the host.

SipA, SopA, SopB, SopD and SopE2 effector proteins of Salmonella enterica serovar Typhimurium are synthesized at late stages of infection in mice

“…Here, we demonstrate that SopD is still present in bacteria infecting MLNs and spleens during late stages of murine salmonellosis. These results are in complete agreement with those reported earlier that show that sopD mutants of serovar Typhimurium are significantly reduced in their ability to replicate in the mouse spleen (Jiang et al, 2004).…”

The ancestral SgrS RNA discriminates horizontally acquired Salmonella mRNAs through a single G-U wobble pair

“…This finding would be consistent with a virulence-associated function of SgrS specific to enteric pathogens with lifestyles that involved colonization and invasion of the inflamed gut epithelium. SopD is known as a general virulence factor, with multiple roles in the development of gastroenteritis, replication in mouse macrophages, and systemic virulence of Salmonella (35,54). SopD also acts as a dual effector delivered by both the SPI-1 and SPI-2 T3SSs that is expressed at later stages of infection when other SPI-1 effectors are no longer produced (22).…”

“…Generally, gene duplication events play important roles in the evolution of new biological functions (60), and HGT genes show a higher propensity than indigenous genes to undergo duplication (61). In Salmonella, additional effector protein pairs, such as SifA and SifB, resulted from gene duplication (35), and it will be interesting to see whether these pairs are also under selective sRNA-mediated control.…”

“…Salmonella encodes an additional effector protein, SopD2, that is 42% identical to SopD (22). Only S. enterica species that are very closely related to the ancestral S. bongori lack this effector, indicating that sopD2 arose from an early duplication of sopD and was followed by evolution to a divergent function (35). Intriguingly, the SgrS target site is almost identical within sopD and sopD2 (SI Appendix, Fig.…”

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

“…SopD acts cooperatively with SopB in the induction of membrane fission and macropinosome formation during Salmonella invasion [274]. It also contributes to virulence during systemic infection of mice and to optimal replication in macrophages, suggesting that SopD contributes not only to early but also to late stages of disease [275]. Both SopD and SopD2 bind with membranes but using different mechanisms.…”