SopD acts cooperatively with SopB during Salmonella enterica serovar Typhimurium invasion

Abstract

SummaryThe intracellular bacterial pathogen, Salmonella enterica serovar Typhimurium (S. typhimurium), causes disease in a variety of hosts. To invade and replicate in host cells, these bacteria subvert host molecular machinery using bacterial proteins, called effectors, which they translocate into host cells using specialized protein delivery systems. One of these effectors, SopD, contributes to gastroenteritis, systemic virulence and persistence of S. typhimurium in animal models of infection. Recently, SopD has been implicated in invasion of polarized epithelial cells and here we investigate the features of SopD-mediated invasion. We show that SopD plays a role in membrane fission and macropinosome formation during S. typhimurium invasion, events previously shown to be mediated by the SopB effector. We further demonstrate that SopD acts cooperatively with SopB to promote these events during invasion. Using live cell imaging we show that a SopD-GFP fusion does not localize to HeLa cell cytosol as previously described, but instead is membrane associated. Upon S. typhimurium infection of these cells, SopD-GFP is recruited to the invasion site, and this recruitment required the phosphatase activity of SopB. Our findings demonstrate a role for SopD in manipulation of host-cell membrane during S. typhimurium invasion and reveal the nature of its cooperative action with SopB.

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).…”

“…The sopD2 gene is not present in the ancestral S. bongori strain (22), and the duplication event at which sopD gave rise to sopD2 likely occurred after or concomitant with the acquisition of major pathogenicity island SPI-2 (55); in other words, it happened very recently on the timescale of enterobacterial evolution. Nonetheless, the sopD and sopD2 genes have already diverged sufficiently to serve distinct functions in host-pathogen interplay (54,56) as well as differ with respect to their own transcriptional control (57,58). Perhaps the selective SgrS-mediated repression of sopD fostered the func-tional diversification of the two genes.…”

The Salmonella-containing vacuole—Moving with the times

“…Nonetheless, since PIs are involved either directly or indirectly in all eukaryotic cell processes, it is likely that SopB activity in the SCV membrane has additional pleiotropic effects [34]. Another T3SS1 effector that is expressed following invasion is SopD [35], a protein that may act cooperatively with SopB at least during initial formation of the phagosome [36]. Lastly, SipA is an actin binding protein that has recently been shown to induce late endosome redistribution in infected cells and also to cooperate with the T3SS2 effector SifA to maintain SCV positioning at late time points [27].…”

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

“…Together with SipA, SopA, SopB, and SopE2 is a major virulence factor responsible for diarrhea during S. enterica serovar Typhimurium infection of calves [229] that contributes to invasion of epithelial cells [256]. 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].…”