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

Mutations in the gyrA and parC genes of quinolone-resistant Neisseria gonorrhoeae isolates in India
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DOI:
10.1016/j.ijantimicag.2012.08.007
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发表时间:
2012-12-01
影响因子:
10.8
通讯作者:
Risbud, Arun
Risbud, Arun
中科院分区:
医学2区
文献类型:
--
作者:
Kulkarni, Sangeeta;Bala, Manju;Risbud, Arun

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据报道,最近印度和世界各地的耐喹诺酮类淋病奈瑟菌分离株数量急剧增加。本研究旨在鉴定和描述对六种不同喹诺酮类抗生素耐药的淋病奈瑟菌的gyrA和parC基因突变。2007-2009年期间,从就诊于性传播疾病诊所的病人身上总共获得64株淋病奈瑟菌临床分离株(新德里,35株;浦那,16株;孟买,6株;海德拉巴,6株;那格浦尔,1株)。采用Etest检测药物敏感性,测序分析gyrA和parC的突变模式。所有菌株对不同喹诺酮类药物的耐药率从17.2%(加替沙星)到98.4%(氧氟沙星和诺氟沙星)不等。gyrA和parC的测序结果显示,100%的菌株存在gyrA突变,46.9%的菌株同时存在gyrA和parC突变。所有菌株均在Ser-91 -> - Phe、Ser-91 -> - Thr和Asp-95位点出现单或双突变。gyrA中的Gly/Asn和parC中的glly -91 -> Gly。Asp-95 -> Asn突变在新德里分离株中最为普遍,而Asp-95 -> Asn突变在新德里分离株中最为普遍。Gly在浦那分离株中流行。菌株被分为8种不同的突变模式。最低抑菌浓度高(>= 8 μ g/mL)的耐药菌株gyrA和parC均发生突变。gyrA和parC突变株的比例差异有统计学意义(P < 0.001)。Asp-95 -> Asn突变仅局限于浦那菌株。这些结果表明,喹诺酮靶酶的突变可能导致这些分离株出现高水平耐药性。(C) 2012 Elsevier B.V.与International Society of Chemotherapy。版权所有。
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 mu g/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. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.