Taking the host cell hostage

Abstract

Enteropathogenic Escherichia coli (EPEC) is a major cause of infant diarrhea in developing countries. This bacterium causes a characteristic lesion on epithelial cells known as ‘attaching and effacing’ (AE). In these lesions, the epithelial cell rearranges its cytoskeleton in response to bacterial signals, the microvilli are destroyed and pedestal-like structures are formed, above which the bacteria adheres tightly to the epithelial cell.The pedestal structures are formed in response to bacterial stimuli that induce localized actin rearrangements. In the absence of the adhesin intimin and/or Tir, its receptor, these pedestals are not completely formed. Now, Kalman and collaborators1xEnteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Kalman, D. et al. Nat. Cell Biol. 1999; 1: 389–391Crossref | PubMedSee all References1 have shown that pedestal formation depends on localized recruitment and activation of two host-cell factors involved in actin polymerization: the heptameric Arp2/3 complex (Arp2/3c), and members of the Wiskott–Aldrich syndrome (WAS) family of proteins (WASP and N-WASP). WASP binds to and activates Arp2/3c and activated Arp2/3c nucleates actin polymerization. Recruitment of Arp2/3c depends on WASP and recruitment of WASP depends on its GTPase-binding domain (GBD), suggesting the involvement of a Rho family GTPase.Kalman et al. propose a model for pedestal formation in response to EPEC adherence, in which EPEC adheres and translocates Tir to the host cell by a type III secretion system. Tir is inserted into the host cell membrane, binds to intimin and directly or indirectly recruits and activates a host GTPase of the Chp subfamily. The Chp-like GTPase recruits WASP by binding the GBD domain of this protein, and WASP then recruits and activates Arp2/3c, stimulating actin nucleation and polymerization, driving membrane protusion and pedestal formation. Pedestal formation by EPEC therefore provides an excellent example of a pathogen recruiting host cell proteins for its own advantage.