Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges

Abstract

SUMMARY The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks -dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as “silent pathogens” with the capacity to emerge as “pathobionts” for the development of inflammatory bowel disease and intestinal carcinogenesis.

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

“…The use of ABU E. coli as a prophylactic agent could address important concerns about antibiotic resistance in patients with UTI recalcitrant to treatment with currently available antibiotics. In the case of VR50, its capacity to express Afa, which contributes to chronic pyelonephritis (77,95) and recurrent cystitis (96), suggests that it would not constitute a suitable prophylactic ABU strain for human use.…”

“…The Afa (and Dr) adhesins comprise a family of surface-located factors encoded by the afa (67)(68)(69)(70)(71), dra (72,73), and daa (74,75) operons. These operons possess similar genetic structures and have been associated with E. coli strains of diarrheagenic and UTI origin (76,77). Many Afa adhesins recognize as a receptor the decay-accelerating factor (DAF), a complement-regulatory protein present on the surfaces of a range of human epithelial cells (including epithelial cells of the urinary tract) (78,79).…”

A gastrointestinal anti-infectious biotherapeutic agent: the heat-treated Lactobacillus LB

“…Coconnier et al [1993aCoconnier et al [ , 1993bCoconnier et al [ , 1998] Secreted molecules of Lactobacillus LB at a subbactericidal concentration promote a decrease in the attachment of diarrhoea-associated Afa/Dr DAEC strain C1845 at the brush border of enterocyte-like Caco-2 cells [Liévin- Le Moal et al 2002], indicating an activity at the level of the interaction between the F1848 bacterial adhesin and the brush border membrane-associated receptors of this adhesin, i.e. the decayaccelerating factor and members of the human carcinoembryonic-antigen-related cell-adhesion molecule family [Servin, 2014] (Table 1). …”

A retrospective study of antibiotic sensitivity pattern of uropathogens in the Federal Capital Territory, Nigeria

“…Microorganisms can reach the urinary tract by haematogenous (Daoud and Afif, 2011;Servin, 2014) or lymphatic spread (Kaper et al, 2004) via interaction between bacteria virulence and the host. Approximately 60% of all women will have a UTI during their lifetime (Daoud and Afif, 2011;Foxman, 2003).…”