Topology and function of translocated EspZ

Abstract

EspZ and Tir are essential virulence effectorsof enteropathogenic Escherichia coli (EPEC). EspZ, the second translocated effector,has been suggested to antagonize host cell death induced by the firsttranslocated effector,Tir (translocated intimin receptor). Another characteristic of EspZ is its localization to host mitochondria. However, studies that explored the mitochondrial localization of EspZ have examined the ectopically expressed effectorand not the more physiologically relevant translocated effector.Here, we confirmedthe membrane topology of translocated EspZ at infection sites and the involvement of Tir in confiningits localization to these sites. Unlike the ectopically expressed EspZ, the translocated EspZ did not colocalize with mitochondrial markers. Moreover, no correlation has been found between the capacity of ectopically expressed EspZ to target mitochondria and the ability of translocated EspZ to protect against cell death. Translocated EspZ may have to some extent diminished F-actin pedestal formation induced by Tir but has a marked effecton protecting against host cell death and on promoting host colonization by the bacteria. Taken together, our results suggest that EspZ plays an essential role in facilitating bacterial colonization, likely by antagonizing cell death mediated by Tir at the onset of bacterial infection. This activity of EspZ, which occurs by targeting host membrane components at infection sites, and not mitochondria, may contribute to successful bacterial colonization of the infected intestine.