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

Abstract

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.

Overexpression of an ABC transporter and mutations of GyrA, GyrB, and ParC in contributing to high-level ciprofloxacin resistance in Streptococcus suis type 2

“…Only one strain had a single mutation in GyrB without mutations in GyrA, ParC, or ParE. The resistance mutations in GyrA and ParC in our strains occurred at the expected hot spots (GyrA-S81Y; ParC-S79Y), which are generally similar to those reported by Escudero et al (13) and those in other Gram-positive bacteria, such as S. aureus, S. pneumoniae, S. pyogenes, and E. faecium (18,(24)(25)(26)(27). It has already been demonstrated that QRDR alterations in GyrB and ParE are associated with fl uoroquinolone resistance in Gram-positive bacteria such as S. aureus, S. pneumoniae, and E. faecium (25,27,28), but this has not been reported in S. suis.…”

Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada

“…Prior to the introduction of gatifloxacin and moxifloxacin, all isolates with mutations observed in the QRDRs of S. pneumoniae had mutations in the parC gene (3,10). Since the introduction of gatifloxacin and moxifloxacin, the number of isolates with parC mutations has remained stable, but there has been an increase in the proportion of isolates with gyrA-only mutations (12,13,24).…”

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

“…High-level resistance results from additional point mutations in the DNA gyrase (gyrA and gyrB) genes (521). These point mutations may be acquired by spontaneous mutation within the QRDR or via horizontal gene transfer (527). The subsequent clonal expansion of resistant strains has contributed to rapid increases in the prevalences of fluoroquinolone-resistant GAS isolates in recent years (521).…”