Molecular epidemiology of the iron utilization genes of enteroaggregative Escherichia coli

Enteroaggregative Escherichia coli (EAEC) strains are etiologic agents of acute and persistent diarrhea. In this study, the results of phenotypic assays suggested that EAEC strains possess specialized iron acquisition systems. Genes required for the synthesis (iucA) or transport (fepC) of siderophores, and genes encoding siderophore (fyuA, ireA, and iroN) or heme transport (chu) receptors or hemoglobin proteases (pic and hbp), were sought in EAEC strains which have been characterized with respect to known virulence genes and phylogeny. The chuA, iucA, fyuA, fepC, and pic genes were detected in 33, 76.2, 85.7, 33, and 61.9% of these EAEC strains, respectively, and the other genes were absent. The majority of EAEC strains possessed genes encoding multiple iron transport systems, and there was no phylogenetic correlation in the distribution of the majority of these loci, as is typical for EAEC. The notable exceptions were chuA and fepC (which is associated with the prrA-modA-fepC pathogenicity island); these genes were restricted to the EAEC2 and DAEC2 phylogenetic groups, which could represent pathogenic subsets. When collections of EAEC strains isolated during case-control studies in Nigeria and Brazil were examined, no association of the presence of either chuA or iucA alone with diarrhea was seen, but both genes together were present in significantly more strains from cases than from controls in the Nigerian collection (P < 0.05). It is possible that the presence of both genes marks at least some virulent strains. The data also demonstrate geographical variation in the association of iron utilization genes with disease in EAEC.