Enteropathogenic Escherichia coli (EPEC) attachment to epithelial cells: exploiting the host cell cytoskeleton from the outside

Abstract

SummaryEnteropathogenic Escherichia coli (EPEC), a leading cause of human infantile diarrhoea, is the prototype for a family of intestinal bacterial pathogens that induce attaching and effacing (A/E) lesions on host cells. A/E lesions are characterized by localized effacement of the brush border of enterocytes, intimate bacterial attachment and pedestal formation beneath the adherent bacteria. As a result of some recent breakthrough discoveries, EPEC has now emerged as a fascinating paradigm for the study of host±pathogen interactions and cytoskeletal rearrangements that occur at the host cell membrane. EPEC uses a type III secretion machinery to attach to epithelial cells, translocating its own receptor for intimate attachment, Tir, into the host cell, which then binds to intimin on the bacterial surface. Studies of EPECinduced cytoskeletal rearrangements have begun to provide clues as to the mechanisms used by this pathogen to subvert the host cell cytoskeleton and signalling pathways. These ®ndings have unravelled new ways by which pathogenic bacteria exploit host processes from the cell surface and have shed new light on how EPEC might cause diarrhoea. EPEC, a model extracellular pathogenAmong the many themes in bacterial pathogenesis, determining how bacteria interact with host cells, including subversion of the cellular cytoskeleton and signal transduction pathways, remains of major interest. Most of the pathogens for which these aspects have been extensively studied, such as Salmonella, Shigella and Listeria species, illustrate that pathogens have evolved strategies to hijack the host cell machinery for invasive purposes. They use the intestinal barrier as an entry site, exploiting the target host cell cytoskeletal machinery to trigger their uptake by non-phagocytic cells, thereby gaining access to the host. Enteropathogenic Escherichia coli (EPEC), a major cause of diarrhoea in the developing world, colonizes the intestinal epithelial surface and exerts its pathologic effects by intimately attaching to the surface of enterocytes, causing histopathological alterations called the attaching/effacing (A/E) lesion. A/E lesions result from degeneration of the enterocyte brush border through the reorganization of the underlying cytoskeleton. This is triggered by bacteria attached to the surface and leads to the localized loss of microvilli and the formation of actin-rich pedestals upon which EPEC reside (Frankel et al., 1998a). Several other pathogens, such as enterohaemorrhagic E. coli (EHEC), which is associated with haemolytic±uraemic syndrome, Citrobacter rodentium and Hafnia alvei, also induce A/E lesion formation upon infection, but EPEC has been the most well studied of these pathogens and thus serves as the paradigm.Like several Gram-negative animal and plant pathogens, EPEC possesses a type III secretion machinery, which is designed to secrete key virulence factors and directly inject some of them into the host cell cytosol by functioning as a`molecular syringe ' (Hueck, 1998). Recently, some new and s...

Quorum sensing in bacterial virulence

“…This important virulence determinant is required for the formation of the characteristic Quorum sensing in bacterial virulence -a review attaching and effacing (AE) lesions caused by these pathogens (Celli et al, 2000). Additionally, transcriptomic studies have revealed that LuxS is a global regulator in EHEC, controlling the expression of over 400 genes (DeLisa et al, 2001;Sperandio et al, 2001).…”

Molecular and phenotypic typing of enteropathogenic Escherichia coli isolated in childhood acute diarrhea in Abuja, Nigeria

“…This lesion is the direct consequence of an adhesin known as intimin that allows the E. coli to adhere to the intestinal epithelium of its host cells [6]. Its adherence to the intestinal mucosa causes a rearrangement of the actin in the host cell, resulting in significant deformation [7]. However, the exact mechanisms of diarrhea in EPEC infection are not completely understood [8,2].…”

Mechanism underlying inhibition of intestinal apical Cl–/OH– exchange following infection with enteropathogenic E. coli

“…Enteropathogenic E. coli (EPEC) is a food-borne pathogen and a major cause of watery infantile diarrhea worldwide that is associated with high rates of morbidity and mortality. A unique feature of EPEC is that it neither expresses toxins nor is invasive but instead attaches intimately to host intestinal epithelial cells (3,4). The pathogenicity island of EPEC houses a number of virulence proteins including those of a type III secretion system (TTSS) through which bacteria directly deliver their proteins into the host cell (5,6).…”