Pathogenesis of Afa/Dr Diffusely AdheringEscherichia coli

Abstract

Over the last few years, dramatic increases in our knowledge about diffusely adhering Escherichia coli (DAEC) pathogenesis have taken place. The typical class of DAEC includes E. coli strains harboring AfaE-I, AfaE-II, AfaE-III, AfaE-V, Dr, Dr-II, F1845, and NFA-I adhesins (Afa/Dr DAEC); these strains (i) have an identical genetic organization and (ii) allow binding to human decay-accelerating factor (DAF) (Afa/DrDAF subclass) or carcinoembryonic antigen (CEA) (Afa/DrCEA subclass). The atypical class of DAEC includes two subclasses of strains; the atypical subclass 1 includes E. coli strains that express AfaE-VII, AfaE-VIII, AAF-I, AAF-II, and AAF-III adhesins, which (i) have an identical genetic organization and (ii) do not bind to human DAF, and the atypical subclass 2 includes E. coli strains that harbor Afa/Dr adhesins or others adhesins promoting diffuse adhesion, together with pathogenicity islands such as the LEE pathogenicity island (DA-EPEC). In this review, the focus is on Afa/Dr DAEC strains that have been found to be associated with urinary tract infections and with enteric infection. The review aims to provide a broad overview and update of the virulence aspects of these intriguing pathogens. Epidemiological studies, diagnostic techniques, characteristic molecular features of Afa/Dr operons, and the respective role of Afa/Dr adhesins and invasins in pathogenesis are described. Following the recognition of membrane-bound receptors, including type IV collagen, DAF, CEACAM1, CEA, and CEACAM6, by Afa/Dr adhesins, activation of signal transduction pathways leads to structural and functional injuries at brush border and junctional domains and to proinflammatory responses in polarized intestinal cells. In addition, uropathogenic Afa/Dr DAEC strains, following recognition of β1 integrin as a receptor, enter epithelial cells by a zipper-like, raft- and microtubule-dependent mechanism. Finally, the presence of other, unknown virulence factors and the way that an Afa/Dr DAEC strain emerges from the human intestinal microbiota as a “silent pathogen” are discussed

Escherichia coli virulence factors

“…The receptor for most afimbrial adhesins produced by human strains is the protein moiety of the Decay-Accelerating factor (DAF), a glycoprotein distributed on human haemopoeitic endothelial, intestinal and urinary cells. On the other hand the only so far recognized afimbrial adhesin produced by pathogenic E. coli from animals (Afa-VIII, related to the M afimbrial adhesin of some human UPEC) does not recognize DAF as a receptor and does not adhere to Hep-II or HeLa cells (Lalioui et al, 1999;Le Bouguénec and Bertin, 1999;Mainil, 2003aMainil, , 2005aServin, 2005). Other receptors for Afa and Dr adhesins of human DAEC are type IV collagen and CEACAMs (CarcinoEmbryonic Antigens-related CellAdhesion Molecules) (Servin, 2005).…”

“…On the other hand the only so far recognized afimbrial adhesin produced by pathogenic E. coli from animals (Afa-VIII, related to the M afimbrial adhesin of some human UPEC) does not recognize DAF as a receptor and does not adhere to Hep-II or HeLa cells (Lalioui et al, 1999;Le Bouguénec and Bertin, 1999;Mainil, 2003aMainil, , 2005aServin, 2005). Other receptors for Afa and Dr adhesins of human DAEC are type IV collagen and CEACAMs (CarcinoEmbryonic Antigens-related CellAdhesion Molecules) (Servin, 2005). The DAEC strains are associated with urinary tract (UPEC), intestinal tract (DEC) and invasive (SePEC) infections in humans, different other mammalian species and poultry (APEC) ( Table 1) (Mainil et al, 1997(Mainil et al, , 2001Le Bouguénec and Bertin, 1999;Gérardin et al, 2000;Stordeur et al, 2002;Servin, 2005).…”

“…Those haemagglutinins actually form a family of genetically related different adhesins, the AFimbrial adhesin (Afa) family regrouping Afa, Dr, M, Nfa, F1845 and AAF variants. Afimbrial adhesins of the Afa family are encoded by plasmid-or chromosome-located genes, according to the variant, but also sometimes within one variant (Law and Chart, 1998;Le Bouguénec and Bertin, 1999;Mainil, 2003aMainil, , 2005aServin, 2005;Harrington et al, 2006). While some members of the family are true afimbrial adhesins (Afa, Dr, M), others form small fibrillae (F1845, AAF), and still others capsule-like structures surrounding the bacterial cell (Nfa).…”

“…With the exception of AAF-positive strains, afimbrial adhesin-producing E. coli display a diffuse adherence (DAEC) pattern on cells in cultures, Hep-II, HeLa, or MDCK, according to the variant (Scaletsky et al, 1984;Le Bouguénec and Bertin, 1999;Servin, 2005). The receptor for most afimbrial adhesins produced by human strains is the protein moiety of the Decay-Accelerating factor (DAF), a glycoprotein distributed on human haemopoeitic endothelial, intestinal and urinary cells.…”

“…The structure of the true afimbrial adhesins can be compared to truncated fimbriae with no major subunit, but only the minor subunits of the basis and the adhesin subunit. One of the minor-like subunits is an invasin participating to the invasion of cells in cultures (Le Bouguénec and Bertin, 1999;Servin, 2005).…”