<i>Neisseria gonorrhoeae</i> acquires mutations in analogous regions of gyrA and parC in fluoroquinolone‐resistant isolates

Abstract

<jats:title>Summary</jats:title><jats:p> <jats:italic>Neisseria gonorrhoeae</jats:italic> homologues of <jats:italic>gyrA</jats:italic> and <jats:italic>parC</jats:italic> have been identified using hybridization probes generated from conserved regions of diverse <jats:italic>gyrA</jats:italic> genes. These genes have been tentatively identified as <jats:italic>gyrA</jats:italic> and <jats:italic>parC</jats:italic>, based on predicted amino acid sequence homologies to known GyrA homologues from numerous bacterial species and to ParC from <jats:italic>Escherichia coli</jats:italic> and <jats:italic>Salmonella typhimurium.</jats:italic> The <jats:italic>gyrA</jats:italic> gene maps to a physical location distant from the <jats:italic>gyrB</jats:italic> locus on the gonococcal chromosome, which is similar to the situation found in <jats:italic>E. coli.</jats:italic> The <jats:italic>parC</jats:italic> gene is not closely linked (i.e. greater than 9 kb) to an identifiable <jats:italic>parE</jats:italic> gene in <jats:italic>N. gonorrhoeae.</jats:italic> The gonococcal GyrA is slightly larger than its <jats:italic>E. coli</jats:italic> homologue and contains several small insertions near the O‐terminus of the predicted open reading frame. A series of ciprofloxacin‐resistant mutants were selected by passage of <jats:italic>N. gonorrhoeae</jats:italic> on increasing concentrations of the antibiotic. Sequential passage resulted in the selection of isolates with minimum inhibitory concentrations approximately 10000‐fold higher than the parental strain. Mutations within <jats:italic>gyrA</jats:italic> resulted in low to moderate levels of resistance, while strains with high‐level resistance acquired analogous mutations in both <jats:italic>gyrA</jats:italic> and <jats:italic>parC.</jats:italic> Resistance mutations were readily transferred between <jats:italic>N. gonorrhoeae</jats:italic> strains by transformation. The frequencies of transformation, resulting in different levels of ciprofloxacin resistance, further support the notion that both gyrA and parC genes are invoived in the establishment of extreme levels of ciprofloxacin resistance.</jats:p>

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