SopE and SopE2 from Salmonella typhimurium Activate Different Sets of RhoGTPases of the Host Cell

Abstract

The bacterial enteropathogen Salmonella typhimurium employs a specialized type III secretion system to inject toxins into host cells, which trigger signaling cascades leading to cell death in macrophages, secretion of pro-inflammatory cytokines, or rearrangements of the host cell cytoskeleton and thus to bacterial invasion. Two of the injected toxins, SopE and the 69% identical protein SopE2, are highly efficient guanine nucleotide exchange factors for the RhoGTPase Cdc42 of the host cell. However, it has been a puzzle why S. typhimurium might employ two toxins with redundant function. We hypothesized that SopE and SopE2 might have different specificities for certain host cellular RhoGTPases. In vitro guanine nucleotide exchange assays and surface plasmon resonance measurements revealed that SopE is an efficient guanine nucleotide exchange factor for Cdc42 and Rac1, whereas SopE2 was interacting efficiently only with Cdc42, but not with Rac1. Affinity precipitation of Cdc42⅐GTP and Rac1⅐GTP from lysates and characteristic cytoskeletal rearrangements of infected tissue culture cells confirmed that SopE is highly efficient at activating Cdc42 and Rac1 in vivo, whereas SopE2 was efficiently activating Cdc42, but not Rac1. We conclude that the translocated effector proteins SopE and SopE2 allow S. typhimurium to specifically activate different sets of RhoGTPase signaling cascades.

Rck of Salmonella enterica, subspecies enterica serovar Enteritidis, mediates Zipper-like internalization

“…The role of these signaling molecules is however not specific to the Zipper mechanism, as their role has also been described in Trigger entry processes [32][33][34]. For example, the T3SS-1 effector SopE activates Cdc42 and Rac by mimicking the action of eukaryotic G-nucleotide exchange factors [35], remodeling the cytoskeleton and altering gene expression during Salmonella T3SS-1-dependent invasion. Then, Cdc42 activates members of the WASP family, whereas Scar/WAVE is activated by Rac during Salmonella T3SS-1-dependent invasion.…”

The Different Strategies Used by Salmonella to Invade Host Cells

“…Their activation induces actin polymerization by stimulating downstream cellular proteins such as N-WASP, WAVE and WASH which activate the Arp2/3 nucleator complex (Buchwald et al, 2002;Schlumberger et al, 2003). SopE specifically targets the Rho GTPases Rac and Cdc42 in vitro whereas SopE2 only activates Cdc42 (Friebel et al, 2001). The role of Rac in Salmonella T3SS-1-dependent entry is well characterized but the role of Cdc42 is controversial.…”

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

“…This gene encodes a protein, SopE2, that is 69% identical to SopE and also acts as an efficient GEF for Cdc42 [26,285] but in contrast with SopE, not for Rac1, suggesting that these two similar effectors can activate different sets of Rho GTPases signaling cascades [286]. Like SopE, SopE2 has been implicated in the pathogenesis of diarrhea and enteritis associated with Salmonella infection in calves [229] and in streptomycin-pretreated mice [228].…”