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Fluoroquinolone Resistance in Invasive Streptococcus pyogenes Isolates Due to Spontaneous Mutation and Horizontal Gene Transfer

Department of Global Health, Rollins School of Public Health,¹ Division of Infectious Diseases, School of Medicine, Emory University,⁶ Respiratory Diseases Branch, Centers for Disease Control and Prevention,³ Georgia Emerging Infections Program, Atlanta, Georgia,⁵ Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany,² Connecticut Department of Public Health, Hartford, Connecticut⁴

Received 4 July 2005/ Returned for modification 31 October 2005/ Accepted 5 December 2005

Fluoroquinolone resistance in Streptococcus pyogenes has been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistant S. pyogenes isolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions of gyrA and parC were sequenced. In both isolates, there was no evidence for an efflux pump and no mutation in gyrA. Both isolates had an S79F mutation in parC that is known to confer fluoroquinolone resistance. In addition, a D91N mutation in parC, which is not related to fluoroquinolone resistance but is a feature of the parC sequence of Streptococcus dysgalactiae, was found in one isolate. The parC nucleotide sequence of that isolate showed greater diversity than that of S. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer from S. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation from S. 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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