title: Involvement of mismatch repair in the reciprocal control of motility and adherence of uropathogenic Escherichia coli.
abstract: 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.
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Michigan, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Cooper
authors.forename: Lyle A
authors.initials: LA
authors.lastname: Simmons
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D053843:DNA Mismatch Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004927:Escherichia coli Infections / Q000382:microbiology; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000502:physiology; D005407:Flagella / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D051379:Mice; D009068:Movement / Q000502:physiology*; D009154:Mutation; D014552:Urinary Tract Infections / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial