Involvement of Mismatch Repair in the Reciprocal Control of Motility and Adherence of Uropathogenic Escherichia coli
ABSTRACTType 1 fimbriae and flagella, two surface organelles critical for colonization of the urinary tract by uropathogenicEscherichia coli(UPEC), mediate opposing virulence objectives. Type 1 fimbriae facilitate adhesion to mucosal cells and promote bacterial persistence in the urinary tract, while flagella propel bacteria through urine and along mucous layers during ascension to the upper urinary tract. Using a transposon screen of theE. coliCFT073fimlocked-ON (L-ON) mutant, a construct that constitutively expresses type 1 fimbriae and represses motility, we identified six mutants that exhibited a partial restoration of motility. Among these six mutated genes wasmutS, which encodes a component of the methyl-directed mismatch repair (MMR) system. When complemented withmutS in trans, motility was again repressed. To determine whether the MMR system, in general, is involved in this reciprocal control, we characterized the effects of gene deletions of other MMR components on UPEC motility. Isogenic deletions ofmutS,mutH, andmutLwere constructed in both wild-type CFT073 andfimL-ON backgrounds. All MMR mutants showed an increase in motility in the wild-type background, and ΔmutHand ΔmutSmutations increased motility in thefimL-ON background. Cochallenge of the wild-type strain with an MMR-defective strain showed a subtle but significant competitive advantage in the bladder and spleen for the MMR mutant using the murine model of ascending urinary tract infection after 48 h. Our findings demonstrate that the MMR system generally affects the reciprocal regulation of motility and adherence and thus could contribute to UPEC pathogenesis during urinary tract infections.