Fluoroquinolone Resistance in InvasiveStreptococcus pyogenesIsolates Due to Spontaneous Mutation and Horizontal Gene Transfer

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Abstract
Fluoroquinolone resistance inStreptococcus pyogeneshas been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistantS. pyogenesisolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions ofgyrAandparCwere sequenced. In both isolates, there was no evidence for an efflux pump and no mutation ingyrA. Both isolates had an S79F mutation inparCthat is known to confer fluoroquinolone resistance. In addition, a D91N mutation inparC, which is not related to fluoroquinolone resistance but is a feature of theparCsequence ofStreptococcus dysgalactiae, was found in one isolate. TheparCnucleotide sequence of that isolate showed greater diversity than that ofS. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer fromS. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation fromS. dysgalactiae. For the other isolate, we could confirm that it acquired resistance by spontaneous mutation by identifying the susceptible ancestor in an outbreak setting.

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