| Most Escherichia coli are commensal organisms; however, some strains have acquired virulence factors that result in their ability to cause disease. This work was undertaken to explore mechanisms of expression of virulence factors that contribute to disease caused by E. coli serotype O157:H7. Three specific aims were addressed: (I) E. coli O157:H7 causes disease in the human, but not the bovine, host. We therefore hypothesized that E. coli O157:H7 differentially expresses virulence factors in the two hosts. We measured gene expression of six putative virulence genes as compared to one control gene in RNA samples from infected children or experimentally infected cattle. We found evidence that host-specific expression of some virulence factors does occur. (II) We examined the mechanism of regulation of the IrgA Homologue Adhesin (Iha) and found that the ferric uptake regulator protein represses iha transcription in the presence of iron. The role of Iha in iron-uptake was also examined, although we were unable to identify a role for Iha86-24 in uptake of the siderophore enterobactin or the enterobactin precursor 2,3' DHB. (III) We tested the hypothesis that Iha is under diversifying selection. We examined iha sequence from 45 iha-containing E. coli. Dn/Ds for the entire data set was 0.35; when analysis was limited to clonally related strains, Dn/Ds was 1.47. This is strong evidence that Iha undergoes diversifying selection. Together, these specific aims add to the scientific community's understanding of virulence gene expression and evolution in pathogenic bacteria. |
