Mutations in the gyrA and parC genes of quinolone-resistant Neisseria gonorrhoeae isolates in India

Abstract

A dramatic increase in the number of quinolone-resistant Neisseria gonorrhoeae isolates in India and worldwide has been reported recently. This study was undertaken to identify and characterise mutations in the gyrA and parC genes of N. gonorrhoeae resistant to six different quinolone antibiotics. In total, 64 N. gonorrhoeae clinical isolates were obtained during 2007-2009 from patients attending sexually transmitted diseases clinics (New Delhi, 35; Pune, 16; Mumbai, 6; Hyderabad, 6; and Nagpur, 1). Antimicrobial susceptibility was determined by Etest and mutation patterns in gyrA and parC were determined by sequencing analysis. All strains showed varying resistance to different quinolone analogues, ranging from 17.2% (gatifloxacin) to 98.4% (ofloxacin and norfloxacin). Sequencing of gyrA and parC revealed that 100% of strains showed mutations in gyrA and 46.9% showed mutations both in gyrA and parC. All strains showed single or double mutations at Ser-91→Phe, Ser-91→Thr and Asp-95→Gly/Asn in gyrA and at Glu-91→Gly in parC. Asp-95→Asn mutation was the most prevalent in strains isolated from New Delhi, whilst Asp-95→Gly was prevalent in strains isolated from Pune. Strains were categorised into eight different mutation patterns. Resistant strains with high minimum inhibitory concentrations (≥8 μg/mL) showed mutations both in gyrA and parC. The difference in the proportion of strains showing mutations in gyrA and parC was found to be significant (P<0.001). The mutation Asp-95→Asn was restricted to Pune strains only. These results indicate that mutations in quinolone target enzymes may have resulted in the high-level resistance seen in these isolates.