Genomic Islands of Uropathogenic Escherichia coli Contribute to Virulence

Abstract

Uropathogenic Escherichia coli (UPEC) strain CFT073 contains 13 large genomic islands ranging in size from 32 kb to 123 kb. Eleven of these genomic islands were individually deleted from the genome, and nine isogenic mutants were tested for their ability to colonize the CBA/J mouse model of ascending urinary tract infection. Three genomic island mutants (ΔPAI- aspV , ΔPAI- metV , and ΔPAI- asnT ) were significantly outcompeted by wild-type CFT073 in the bladders and/or kidneys following transurethral cochallenge ( P ≤ 0.0139). The PAI- metV mutant also showed significant attenuation in the ability to independently colonize the kidneys ( P = 0.0011). Specific genes within these islands contributed to the observed phenotype, including a previously uncharacterized iron acquisition cluster, fbpABCD (c0294 to c0297 [c0294-97]), autotransporter, picU (c0350), and RTX family exoprotein, tosA (c0363) in the PAI- aspV island. The double deletion mutant with deletions in both copies of the fbp iron acquisition operon (Δc0294-97 Δc2518-15) was significantly outcompeted by wild-type CFT073 in cochallenge. Strains with mutations in a type VI secretion system within the PAI- metV island did not show attenuation. The attenuation of the PAI- metV island was localized to genes c3405-10, encoding a putative phosphotransferase transport system, which is common to UPEC and avian pathogenic E . coli strains but absent from E . coli K-12. We have shown that, in addition to encoding virulence genes, genomic islands contribute to the overall fitness of UPEC strain CFT073 in vivo.