PATHOGENICITY ISLAND SEQUENCES OF PYELONEPHRITOGENIC ESCHERICHIA-COLICFT073 ARE ASSOCIATED WITH VIRULENT UROPATHOGENIC STRAINS

Urinary tract infection is the most frequently diagnosed kidney and ur ologic disease, and Escherichia coli is by hr the most common etiologi c agent. Defined blocks of DNA termed pathogenicity islands have been found in uropathogenic strains to canp genes not generally found in fe cal strains. We have identified one of these regions of DNA within the chromosome of the highly virulent E. coli CFT073, isolated from the b lood and urine of a woman with acute pyelonephritis. This strain, whic h is cytotoxic for cultured renal cells and causes acute pyelonephriti s in transurethrally infected CBA mice, contains two distinct copies o f the pap operon and is hemolytic, One pap operon was localized on a c osmid clone which was used to identify three overlapping cosmid clones , By using restriction mapping, DNA hybridization, sequencing, and PCR amplification, a region of approximately 50 kb was found to be presen t in this uropathogenic strain and to have no corresponding sequences in E. coli K-12. This gene block also carries hemolysin genes hlyCABD. The pathogenicity island begins 7 bp downstream of dadX (catabolic al anine racemase; 26.55 min) and ends at a position in the K-12 genome 7 5 bp downstream of the metV tRNA gene (62.74 min); this suggests that a chromosomal rearrangement las occurred relative to the K-12 linkage map. The junctions of the pathogenicity island mere verified by PCR am plification directly from the genomic DNA of strain CFT073. DNA sequen cing within the boundaries of the junctions revealed genes not previou sly identified in E. coli or in some cases bearing no known homologs. When used as probes for DNA hybridization, these sequences were found significantly mure often in strains associated with the clinical syndr omes of cystitis (82%) and acute pyelonephritis (79%) than in fecal st rains (19%; P < 0.001).