Type 1 fimbriae and flagella, two surface organelles critical for colonization 
of the urinary tract by uropathogenic Escherichia 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 the E. coli CFT073 fim locked-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 was mutS, which encodes a 
component of the methyl-directed mismatch repair (MMR) system. When complemented 
with mutS 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 of mutS, mutH, and mutL were constructed in both wild-type CFT073 and 
fim L-ON backgrounds. All MMR mutants showed an increase in motility in the 
wild-type background, and ΔmutH and ΔmutS mutations increased motility in the 
fim L-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.