title: Conjugation between quinolone-susceptible bacteria can generate mutations in the quinolone resistance-determining region, inducing quinolone resistance.
abstract: Quinolones are an important group of antibacterial agents that can inhibit DNA gyrase and topoisomerase IV activity. DNA gyrase is responsible for maintaining bacteria in a negatively supercoiled state, being composed of subunits A and B. Topoisomerase IV is a homologue of DNA gyrase and consists of two subunits codified by the parC and parE genes. Mutations in gyrA and gyrB of DNA gyrase may confer resistance to quinolones, and the majority of resistant strains show mutations between positions 67 and 106 of gyrA, a region denoted the quinolone resistance-determining region (QRDR). The most frequent substitutions occur at positions 83 and 87, but little is known about the mechanisms promoting appearance of mutations in the QRDR. The present study proposes that some mutations in the QRDR could be generated as a result of the natural mechanism of conjugation between bacteria in their natural habitat. This event was observed following conjugation in vitro of two different isolates of quinolone-susceptible Pseudomonas aeruginosa, which transferred plasmids of different molecular weights to a recipient strain of Escherichia coli (HB101), also quinolone-susceptible, generating two different transconjugants that presented mutations in DNA gyrase and acquisition of resistance to all quinolones tested.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Av. do Café, s/n, Monte Alegre, Riberão Preto, SP CEP: 14040-903, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Pitondo-Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Av. do Café, s/n, Monte Alegre, Riberão Preto, SP CEP: 14040-903, Brazil.
authors.forename: Vinicius Vicente
authors.initials: VV
authors.lastname: Martins
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Av. do Café, s/n, Monte Alegre, Riberão Preto, SP CEP: 14040-903, Brazil.
authors.forename: Carolina Fávero da
authors.initials: CF
authors.lastname: Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Av. do Café, s/n, Monte Alegre, Riberão Preto, SP CEP: 14040-903, Brazil. Electronic address: elianags@usp.br.
authors.forename: Eliana Guedes
authors.initials: EG
authors.lastname: Stehling
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D003227:Conjugation, Genetic; D017931:DNA Primers; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D005798:Genes, Bacterial; D009154:Mutation; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D017931:DNA Primers; D015363:Quinolones
keywords: Conjugation; Mutations; QRDR; Quinolones; Resistance