Rate of Occurrence and Pathogenic Effect of Enteroaggregative Escherichia coli Virulence Factors in International Travelers

Abstract

One or more putative enteroaggregative Escherichia coli (EAEC) virulence factors (aggA, aggR, aspU, or aafA) were identified in 60 (70%) of 86 EAEC isolates from travelers with diarrhea compared with a rate of 7 (8%) of 90 in patients with diarrhea who were infected with nonadherent E. coli (odds ratio, 27.36; 95% confidence interval, 11.30 to 65.91). The presence of aggR or one or more virulence factors in EAEC from patients with diarrhea was associated with a statistically increased concentration of interleukin-8 (IL-8) in feces compared with that in EAEC negative for these factors: for aggR positive (9 of 12 [75%]; median, 800 pg/ml) versus aggR negative (5 of 18 [28%]; median, 0), P < 0.05; and for isolates positive for >1 virulence factor (13 of 21 [62%]; median, 360 pg/ml) versus those negative for >1 virulence factor (1 of 9 [11%]; median, 0), P < 0.05. Other fecal cytokines (IL-1␤ and IL-1ra) were found in increased concentrations (P < 0.05 when at least one EAEC virulence factor was present compared with the concentrations when EAEC negative for multiple virulence factors was found in patients with diarrhea. Putative virulence factors were commonly found in EAEC from patients with diarrhea, and the pathogenicity of many strains was suggested by showing an association between the presence of plasmid-borne virulence factors and the presence of fecal cytokines. The different patterns of virulence factors of EAEC revealed several clusters demonstrating diversity among the isolates from the various regions.Enteroaggregative Escherichia coli (EAEC) strains have been identified as a possible important cause of persistent diarrhea in children (17) and adult travelers (1) in developing countries. Strains of EAEC differ in their pathogenicity (16), but the pathophysiology of EAEC diarrhea and the virulence traits that enable the organism to cause diarrhea are not well understood. It has been shown that most EAEC strains possess a 60-to 65-MDa plasmid (designated pAA) which encodes several putative virulence factors, including the AA fimbria characterized as AAF

Interleukin‐8 Secretion by Epithelial Cells Infected with Diffusely Adherent Escherichia coli Possessing Afa Adhesin‐Coding Genes

“…EAggEC, another group of enteroadherent E. coli, have been reported to cause the release of IL-8 from human intestinal epithelial cells. IL-8 was detected in the fecal specimens of infected patients, and the ability of EAggECs to induce IL-8 secretion from epithelial cells correlated with diar- (26,50,51).…”

“…Fecal IL-8 elevation may correlate with the severity of clinical symptoms (26,50,51). In this study, we investigated whether all afa-positive DAEC strains could induce IL-8 secretion from cultured human epithelial cells to the same extent as EAggEC.…”

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

“…EAEC strains have been shown to cause the release of IL-8 from fully differentiated Caco-2 cells (794), an effect mediated by the flagella and flagellin protein (795) and involving p38 MAPK signaling via activation of the TLR5 receptor located in the basolateral domain of the cells (796,797) (Table 6). In addition, plasmid-encoded factors may play a role in EAEC IL-8 induction (798). In EAEC-infected fully differentiated T84 cells, the upregulation of genes encoding IL-8, IL-6, TNF-␣, CXCL1, CXCL3, intercellular adhesion molecule 1 (ICAM-1), GM-CSF, and IL-1␣ has been observed, as a result of the presence of AAF adhesin (799).…”

Characteristics of the enteroaggregative Shiga toxin/verotoxin-producing Escherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany, May to June 2011

“…EAggEC infections are usually associated with watery diarrhoea, which is often persistent [20]. Illness results from a complex interaction between pathogen and host, which implicates the initial adherence of the bacteria to the epithelium of terminal ileum and colon, by virtue of the aggregative adherence fimbriae (characteristic aggregative pattern), followed by a damage/secretion stage manifested by cytokine release, mucosal toxicity, intestinal secretion and induction of mucosal inflammation [22][23][24][25][26]. EAggEC is best known for its role in persistent diarrhoea (>14 days) in infants and children in developing countries.…”