In recent years, some of these potential virulence factors have been described. In addition, some studies have implicated DAEC strains as diarrheal agents only in children older than six months, depending on the study, and in adults. [4, 13–19]. Evidence of a type three secretion system (TTSS) in DAEC Afa/Dr+ isolated from cases of diarrhea in children has been demonstrated by Kyaw et al.. The concomitant presence of Afa/Dr adhesins in these strains suggests that an adhesin-receptor-effector protein mechanism, similar to the one
seen in EPEC (enteropathogenic E. coli), might occur in DAEC. After adhesion and intimate contact, EPEC strains use TTSS to inject effector proteins into the host cell, inducing lesions in the cytoskeleton. Taddei et al. reported the presence of the secreted autotransporter toxin (SAT) belonging to the family of serine protease autotransporters of Enterobacteriaceae selleck screening library (SPATE) in DAEC strains isolated from diarrhea. Guignot et al. have demonstrated that SAT is able to cause lesions on tight junctions of epithelial cells, which in turn may lead to an increase in their permeability. They also found SAT more frequently in DAEC www.selleckchem.com/products/cb-5083.html strains isolated from diarrheic children than from asymptomatic subjects, corroborating the role of SAT as a virulence factor. DAEC strains have demonstrated pro-inflammatory
effects, related to an increased secretion Thalidomide of interleukin-8
by epithelial cells. In T84 cells infected by wild-type strains, basolateral secretion of IL-8 promotes transmigration of polymorphonuclear leukocytes (PMNLs) across the epithelial monolayer . The transmigrated PMNs increase apoptotic rates and reduce phagocytic activity  which can contribute to maintain the inflammatory response without eliminating the pathogen. Some studies [18, 25] have found that the ability of increasing IL-8 secretion in epithelial cells by DAEC strains was associated with diarrhea in children. One characteristic that has not been studied in DAEC is the ability to form biofilms. Although biofilm formation is a widespread phenomenon in bacteria, only recently has the importance of biofilms as a pathogenic factor been demonstrated for E. coli, such as in atypical EPEC strains  and in enteroaggregative E. coli (EAEC). The latter have biofilm formation as the only consensual virulence factor . In a previous study performed in this laboratory , it was found that EAEC biofilms could be enhanced by interaction with a Citrobacter freundii strain isolated concomitantly with EAEC from a diarrheic child. These mixed biofilms seem to be mediated by F pili. Aside from their role in conjugation, F pili have been considered important in establishing E. coli biofilms, in addition to other components like curli and cellulose [29, 30].