Division of Bacteriology, National Veterinary Research and Quarantine Service, Anyang, Gyeonggi-do, Republic of Korea.
Foodborne Pathog Dis. 2011 Nov;8(11):1199-206. doi: 10.1089/fpd.2011.0899. Epub 2011 Aug 30.
The aim of this study was to investigate the prevalence and mechanism of quinolone resistance among selected nontyphoid Salmonella (NTS) isolates. A total of 1279 NTS isolated from food animals (n=692) and humans (n=587) between 1995 and 2009 were investigated by serotyping, antimicrobial susceptibility testing, screening for plasmid-mediated quinolone resistance (PMQR) genes qnr, aac(6')-Ib-cr, and qepA and mutations in the quinolone resistance-determining region (QRDR) of gyrA and parC by PCR, and DNA sequencing. Three hundred thirty (47.7%) of 692 animal isolates and 177 (30.2%) of 587 human isolates were resistant to nalidixic acid. Most animal (94.8%, 313/330) and human (99.4%, 176/177) NTS exhibited decreased ciprofloxacin susceptibility (minimum inhibitory concentration [MIC]: 0.125-2 mg/L). None of them carried qnr or qepA gene. However, aac(6')-Ib was identified in six animal isolates, of which four carried aac(6')-Ib-cr gene. Based on antimicrobial resistance profile, year of isolation, MIC for quinolones and fluoroquinolones, and isolation frequency of serotype, 114 animal and 83 human isolates were tested for QRDR mutations. All contained a single mutation within the QRDR of gyrA at either codon 87 or 83, and 41 of them contained an additional mutation in parC. The most prevalent mutation was Asp87-Tyr (n=107), followed by Asp87-Gly (n=28), Asp87-Asn (n=26), Ser83-Tyr (n=22), and Ser83-Phe (n=14). Point mutations in parC were observed outside the QRDR, which included 40 isolates with Thr57-Ser substitution and 1 Salmonella Typhimurium with a novel Glu51-Lys substitution. In conclusion, a point mutation within the QRDR of gyrA was primarily responsible for quinolone resistance and reduced susceptibility to fluoroquinolones in NTS in Korea. To our knowledge, this is the first report of occurrence of aac(6')-Ib-cr gene among NTS in Korea. The spread of NTS carrying aac(6')-Ib-cr is of serious concern and should be carefully monitored.
本研究旨在调查选定非伤寒沙门氏菌(NTS)分离株中喹诺酮类药物耐药的流行情况和机制。1995 年至 2009 年间,从食品动物(n=692)和人类(n=587)中分离出 1279 株 NTS,通过血清分型、抗菌药物敏感性试验、质粒介导的喹诺酮类药物耐药(PMQR)基因 qnr、aac(6')-Ib-cr 和 qepA 的筛选以及 PCR 和 DNA 测序检测喹诺酮类药物耐药决定区(QRDR)中的突变。692 株动物分离株中有 330 株(47.7%)对萘啶酸耐药,587 株人类分离株中有 177 株(30.2%)对萘啶酸耐药。大多数动物(94.8%,313/330)和人类(99.4%,176/177)NTS 对环丙沙星的敏感性降低(最小抑菌浓度 [MIC]:0.125-2 mg/L)。它们均未携带 qnr 或 qepA 基因。然而,在 6 株动物分离株中鉴定出 aac(6')-Ib,其中 4 株携带 aac(6')-Ib-cr 基因。根据抗菌药物耐药谱、分离年份、喹诺酮类和氟喹诺酮类药物的 MIC 以及血清型的分离频率,对 114 株动物分离株和 83 株人类分离株进行了 QRDR 突变检测。所有分离株的 gyrA 的 QRDR 中均有单个突变,位于密码子 87 或 83,其中 41 株在 parC 中还存在额外的突变。最常见的突变是 Asp87-Tyr(n=107),其次是 Asp87-Gly(n=28)、Asp87-Asn(n=26)、Ser83-Tyr(n=22)和 Ser83-Phe(n=14)。在 parC 中的点突变发生在 QRDR 之外,包括 40 株含有 Thr57-Ser 取代的分离株和 1 株含有新型 Glu51-Lys 取代的鼠伤寒沙门氏菌。综上所述,gyrA 的 QRDR 中的点突变是 NTS 对喹诺酮类药物耐药和对氟喹诺酮类药物敏感性降低的主要原因。据我们所知,这是韩国首次报道 NTS 中存在 aac(6')-Ib-cr 基因。携带 aac(6')-Ib-cr 的 NTS 的传播令人严重关切,应密切监测。