Identification of a Gene Encoding Heat-Resistant Agglutinin in Escherichia coli as a Putative Virulence Factor in Urinary Tract Infection

Abstract

Escherichia coli causes the vast majority of urinary tract infections (UTI) in both ambulatory and hospital patients. Several uropathogenic virulence factors have been identified, but half of all E. coli isolates that cause UTI have none or only one of the known virulence factors. Thus, it is reasonable to presume that other bacterial factors may be important in UTI pathogenesis. In order to find additional uropathogenic E. coli genes, we used genomic subtraction to identify DNA regions present in a uropathogenic strain of E. coli (1128-11). Genomic subtraction yielded 40 tester-specific fragments, including a novel heat-resistant agglutinin ( hra ) gene fragment. hra occurred in 55% of 486 UTI strains compared to 28% of 165 rectal strains ( P = 0.001). The hra gene in 1128-11 was cloned, sequenced, and found to have 91% homology to the hra gene from E. coli meningitis strain RS218. The genetic organization of genes flanking hra in 1128-11 is distinct from the hra found in E. coli strains J96 and RS218. In our UTI and rectal specimen collections, hra was positively associated with a number of known virulence genes, including pathogenicity island genes hly and cnf , which are absent in 1128-11. The presence of hra in 1128-11 independent of hly/cnf suggests multiple mechanisms by which hra can be acquired by pathogenic E. coli strains. The flanking genes suggest that in 1128-11, hra may be part of a novel variant of a pathogenicity island V.