Molecular epidemiology of quinolone resistance in Acinetobacter spp.

Abstract

OBJECTIVE: To determine whether similar mutations to quinolone resistance in the gyrA subunit of DNA gyrase and the parC subunit of topoisomerase IV are occurring independently in genotypically unrelated clinical isolates of Acinetobacter spp., or whether worldwide clonal spread of particular resistant strains is occurring. METHODS: The genotypic relationships of 25 nosocomial isolates of Acinetobacter spp. from 15 locations in 11 different countries worldwide were examined by randomly amplified polymorphic DNA analysis. Quinolone resistance-determining regions of gyrA and parC were amplified by PCR and mutations were analyzed by restriction digestion with Hinfl and DNA sequencing. RESULTS: Twenty-four of the 25 Acinetobacter isolates were genotypically heterogeneous and 12 were resistant to both nalidixic acid and ciprofloxacin. Analysis of conserved gyrA and parC regions showed that all isolates with a ciprofloxacin MIC of 4 mg/L had a substitution of Ser83 with either Leu or Phe in the GyrA protein. Five of six isolates with ciprofloxacin MICs of 64 mg/L had additional substitutions of Ser80 with Leu in the ParC protein. CONCLUSIONS: Similar mutations to quinolone resistance, predominantly at codons 82--83 of gyrA, are occurring independently in genotypically distinct isolates of Acinetobacter spp. from different worldwide locations. Most isolates with high ciprofloxacin MICs also exhibited secondary mutations in parC at codons 79--80.

Multidrug-resistantPseudomonas aeruginosaandAcinetobacter baumannii: resistance mechanisms and implications for therapy

“…It seems that mutations in the genes encoding the Seward and Towner reported that similar mutations in gyrA, predominantly at codons 82-83, occurred in genotypically distinct Acinetobacter spp. isolates collected from different locations worldwide [134]. Most isolates with high ciprofloxacin MICs also exhibited secondary mutations in parC at codons 79-80 [1,134].…”

Infecciones por Acinetobacter baumannii pan-resistente: Consideraciones epidemiológicas y de manejo antimicrobiano actualizado

“…Las fluoroquinolonas tienen una buena actividad sobre Acinetobacter sp, pero la resistencia está aumentando 3,17,18 . Los mecanismos de resistencia se relacionan con mutaciones de la ADNgirasa y la topo-isomerasa IV, blancos específi-cos de tales antibacterianos 74 . La ADN-girasa está compuesta de dos subunidades, codificadas por los genes gyr A y gyr B.…”

“…La topo-isomerasa IV es estructuralmente similar a la ADN-girasa, pero es un blanco secundario de las fluoroquinolonas. Las dos subunidades de la topoisomerasa IV están codificadas por los genes par C y par E 74 . La resistencia en Acinetobacter sp está mediada por mutaciones en los genes gyr A y par C…”

Acinetobacter baumannii : Emergence of a Successful Pathogen

“…Modifications to DNA gyrase or topoisomerase IV through mutations in the gyrA and parC genes have been well described for A. baumannii (220,236,504,581,582). These mutations interfere with target site binding.…”