Comparison of YopE and YopT activities in counteracting host signalling responses to Yersinia pseudotuberculosis infection

Abstract

Pathogenic Yersinia species share a type III secretion system that translocates Yop effector proteins into host cells to counteract signalling responses during infection. Two of these effectors, YopE and YopT, downregulate Rho GTPases by different mechanisms. Here, we investigate whether YopT and YopE are functionally redundant by dissecting the contribution of these two effectors to the pathogenesis of Yersinia pseudotuberculosis in a mouse infection and tissue culture model. Four days after oral infection, a YopE(+) T (-) strain and a YopE(+) T (+) strain colonized spleens of mice at similar levels, suggesting that YopT is not required for virulence. In contrast, spleen colonization by a YopE(-)T(-) strain was significantly reduced. A YopE(-) T (+) strain colonized spleen at levels comparable to those of the YopE(+) T (-) strain, arguing that YopT can promote virulence in the absence of YopE. Infection of HeLa cells with a YopE(-) T(-)H(-)J(-) strain expressing either YopE or YopT showed that YopE had a stronger antiphagocytic activity than YopT. Expression of YopE strongly inhibited activation of JNK, ERK and NFkappaB, and prevented production of IL-8; whereas YopT moderately inhibited these responses. On the other hand, pore formation was inhibited equally by YopE or YopT. In conclusion, YopE is a potent inhibitor of infection-induced signalling cascades, and YopT can only partially compensate for the loss of YopE.