title: Effects of a Mutation in the gyrA Gene on the Virulence of Uropathogenic Escherichia coli.
abstract: Fluoroquinolones are among the drugs most extensively used for the treatment of bacterial infections in human and veterinary medicine. Resistance to quinolones can be chromosome or plasmid mediated. The chromosomal mechanism of resistance is associated with mutations in the DNA gyrase- and topoisomerase IV-encoding genes and mutations in regulatory genes affecting different efflux systems, among others. We studied the role of the acquisition of a mutation in the gyrA gene in the virulence and protein expression of uropathogenic Escherichia coli (UPEC). The HC14366M strain carrying a mutation in the gyrA gene (S83L) was found to lose the capacity to cause cystitis and pyelonephritis mainly due to a decrease in the expression of the fimA, papA, papB, and ompA genes. The levels of expression of the fimA, papB, and ompA genes were recovered on complementing the strain with a plasmid containing the gyrA wild-type gene. However, only a slight recovery was observed in the colonization of the bladder in the GyrA complement strain compared to the mutant strain in a murine model of ascending urinary tract infection. In conclusion, a mutation in the gyrA gene of uropathogenic E. coli reduced the virulence of the bacteria, likely in association with the effect of DNA supercoiling on the expression of several virulence factors and proteins, thereby decreasing their capacity to cause cystitis and pyelonephritis.
authors.affiliation: Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Unit of Infectious Diseases, Microbiology and Preventive Medicine, Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-Céspedes
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Sáez-López
authors.affiliation: University Hospital, Department of Clinical Microbiology, Hvidovre, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Frimodt-Møller
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain sara.soto@cresib.cat.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Soto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003556:Cystitis / Q000382:microbiology; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects / Q000235:genetics*; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D037521:Virulence Factors; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase