Mutation Rate and Evolution of Fluoroquinolone Resistance in Escherichia coli Isolates from Patients with Urinary tract infections
2003 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 47, no 10, 3222-3232 p.Article in journal (Refereed) Published
Escherichia coli strains from patients with uncomplicated urinarytract infections were examined by DNA sequencing for fluoroquinoloneresistance-associated mutations in six genes: gyrA, gyrB, parC,parE, marOR, and acrR. The 54 strains analyzed had a susceptibilityrange distributed across 15 dilutions of the fluoroquinoloneMICs. There was a correlation between the fluoroquinolone MICand the number of resistance mutations that a strain carried,with resistant strains having mutations in two to five of thesegenes. Most resistant strains carried two mutations in gyrAand one mutation in parC. In addition, many resistant strainshad mutations in parE, marOR, and/or acrR. No (resistance) mutationwas found in gyrB. Thus, the evolution of fluoroquinolone resistanceinvolves the accumulation of multiple mutations in several genes.The spontaneous mutation rate in these clinical strains variedby 2 orders of magnitude. A high mutation rate correlated stronglywith a clinical resistance phenotype. This correlation suggeststhat an increased general mutation rate may play a significantrole in the development of high-level resistance to fluoroquinolonesby increasing the rate of accumulation of rare new mutations.
Place, publisher, year, edition, pages
2003. Vol. 47, no 10, 3222-3232 p.
IdentifiersURN: urn:nbn:se:uu:diva-96329DOI: 10.1128/AAC.47.10.3222-3232.2003OAI: oai:DiVA.org:uu-96329DiVA: diva2:170869