The presence of the virulence island containing the usp gene in uropathogenic Escherichia coli is associated with urinary tract infection in an experimental mouse model

Abstract

Purpose: A putative virulence island commonly noted in the genome of uropathogenic Escherichia coli strains has recently been reported. We have observed that the island includes a gene consisting of a protein designated uropathogenic specific protein (usp) and 3 small open reading frames (orfU1-3). In our current study we assessed the importance of the genes located in the putative virulence island in the pathogenesis of urinary tract infection using a mouse pyelonephritis model. Materials and Methods: A total of 427 E. coli strains isolated from the urine of 194, 76 and 107 subjects suffering from cystitis, pyelonephritis and prostatitis, respectively, and 50 isolates from the feces of healthy individuals were examined for genotypes and serotypes. In addition, several recombinant E. coli strains possessing usp and/or orfU1 to 3 were constructed for evaluating the significance of these genes using an experimental pyelonephritis mouse model. Results: The usp was significantly more often associated with uropathogenic E. coli strains (79.4% from cystitis, 93.4% from pyelonephritis and 88.8% from prostatitis) than with fecal E. coli strains from healthy individuals (24%). Furthermore, usp was frequently associated with all common serotypes of uropathogenic E. coli (71.7% to 100%). In challenge experiments using the mouse urinary tract infection model the vector possessing usp significantly enhanced the infectibility of the E. coli host cell, whereas the 3 small proteins at the downstream of usp failed to show the effect. Conclusion: Our results indicate that usp may contribute to the causation of urinary tract infection and may be considered a major virulence determinant of uropathogenic E. coli.