Cytoskeleton-modulating effectors of enteropathogenic and enterohemorrhagic Escherichia coli

Abstract

Cellular morphology is essential in the maintenance of the shape and stability of cells and tissues. It is also extremely important in preventing infectious viruses or bacteria from penetrating organs, which it does by forming tight networks of intracellular cytoskeletal proteins and cell–cell junctions. Many pathogenic bacteria attack the cytoskeletal proteins of target host cells in order to modulate host cell morphology as a means of facilitating further penetration of these bacteria into various organs and preventing their clearance by normal immune systems in the host organism. Owing to the complexity of the various systems that regulate the host cell cytoskeleton, numerous types of virulence factors have been evolved by bacteria in order to interfere with the host cell morphology. It is critical to analyse the roles of these virulence factors in order to understand the mechanisms of defense against bacterial pathogens. Pathogenic Gram-negative bacteria, including enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), possess type III secretion systems (T3SS) or ‘injectisomes’ that efficiently deliver the virulence factors – often called ‘effectors’ or ‘effector proteins’ – directly from the bacterial cell into a host cell. These effectors usually interact with host cell proteins that are involved in modulation of the cytoskeleton and they control or ‘hijack’ the system in order to facilitate various subsequent events in bacterial infection. Some of the effectors from EPEC or EHEC, including Tir, intimin, EspFU, EspB and EspL2, affect the morphologies of actin networks in infected host cells and change the shapes of the cells. Recent advancements have clarified the complex mechanisms that underlie infection by these pathogens. This minireview series summarizes some of the studies focused on particular effector(s) from EHEC and EPEC that affect the actin cytoskeletal networks in host cells. It provides an overview of the morphological alterations engendered by Tir, EspFU and intimin, which are probably the major effectors or virulence factors for EHEC and EPEC. In the first minireview, Campellone introduces an established concept of actin reorganization and pedestal formation regulated by Tir and EspFU. In the second minireview, Tobe introduces another pathway of actin reorganization caused by EspL2, which is a novel class of actin-modulating effectors. The third minireview summarizes recent achievements in understanding the change in actin morphology caused by EspB and various T3SS effectors, which are classified as natively unfolded proteins. This minireview series provides an insight into the complex mechanisms of cytoskeletal morphology changes induced by EPEC and EHEC, and shed light on the underlying problems regarding EPEC and EHEC infections.