Exploitation of host cells by enteropathogenic Escherichia coli

Abstract

Microbial pathogens have evolved many ingenious ways to infect their hosts and cause disease, including the subversion and exploitation of target host cells. One such subversive microbe is enteropathogenic Escherichia coli (EPEC). A major cause of infantile diarrhea in developing countries, EPEC poses a significant health threat to children worldwide. Central to EPEC-mediated disease is its colonization of the intestinal epithelium. After initial adherence, EPEC causes the localized effacement of microvilli and intimately attaches to the host cell surface, forming characteristic attaching and effacing (A/E) lesions. Considered the prototype for a family of A/E lesion-causing bacteria, recent in vitro studies of EPEC have revolutionized our understanding of how these pathogens infect their hosts and cause disease. Intimate attachment requires the type III-mediated secretion of bacterial proteins, several of which are translocated directly into the infected cell, including the bacteria's own receptor (Tir). Binding to this membrane-bound, pathogen-derived protein permits EPEC to intimately attach to mammalian cells. The translocated EPEC proteins also activate signaling pathways within the underlying cell, causing the reorganization of the host actin cytoskeleton and the formation of pedestal-like structures beneath the adherent bacteria. This review explores what is known about EPEC's subversion of mammalian cell functions and how this knowledge has provided novel insights into bacterial pathogenesis and microbe-host interactions. Future studies of A/E pathogens in animal models should provide further insights into how EPEC exploits not only epithelial cells but other host cells, including those of the immune system, to cause diarrheal disease.

Figure 1

Translocation of EPEC-secreted proteins (Esps) occurs through a type III secretion system that forms a pore through EPEC's membranes. Once translocated outside the bacteria, EspA forms a filamentous translocation tube whereas EspB and EspD are inserted into the host cell membrane, putatively forming a pore structure, allowing the passage of other effector proteins, such as Tir into the host cell membrane.

Figure 2

Transmission electron micrograph of A/E lesions in rabbit intestinal epithelial tissue (Peyer's patch) caused by REPEC O103. Bacteria labeled with “B”; pedestal labeled with “P.” (Photograph is courtesy of Ursula Heczko, Biotechnology Laboratory, University of British Columbia.) (×20,000.)

Figure 3

Pedestal formation on epithelial cells induced by enteropathogenic Escherichia coli. Fluorescence microscopy of the EPEC pedestal, triple-labeled for actin (green), EPEC (blue), and Tir (red) (courtesy of Danika Goosney, Biotechnology Laboratory, University of British Columbia). (×1,000.)

Figure 4

The structure of the EPEC pedestal. EPEC intimately attaches to the host cell through intimin-Tir binding. N-WASP and the Arp 2/3 complex are recruited to the pedestal tip, nucleating actin. F-actin, α-actinin, talin, ezrin, and villin are found along the length of the pedestal whereas nonmuscle myosin II and tropomyosin are found at the pedestal base.

Figure 5

Putative mechanisms underlying EPEC induced diarrhea include increased epithelial permeability and alterations in Cl⁻ and HCO₃⁻ ion secretion. Contributing structural changes include loss of absorptive surfaces, reduced tight junction integrity, and tissue damage.