Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains
Detection of grlA and gyrA Mutations in 344 Staphylococcus aureus Strains
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344株金黄色葡萄球菌grlA和gyrA突变的检测
DOI：
10.1128/aac.42.2.236
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发表时间：
1998
影响因子：
4.9
通讯作者：
Kenichi Sato
中科院分区：
文献类型：
--
作者：
Tong Wang;Mayumi Tanaka;Kenichi Sato
摘要通过单链构象多态性分析、限制性片段长度分析和直接测序相结合的方法，对1994年在日本分离的344株金黄色葡萄球菌临床菌株的grlA和gyrA基因突变进行了鉴定，以确定其与氟喹诺酮耐药的可能关系。204株（59.3%）grlA基因存在5种单点突变和4种双点突变。188株（54.7%）gyrA基因存在4种单点突变和4种双点突变。其中TCC→TTC或TAC的grlA突变（Ser-80→Phe或Tyr）和TCA→TTA的gyrA突变（Ser-84→Leu）分别占39.8%和35.9%。grlA的CAT→CAC（His-77 [沉默]）、TCA→CCA（Ser-81→Pro）和ATA→ATT（Ile-100 [沉默]）点突变是新的，gyrA的GAC→GGC（Asp-73→Gly）变化也是新的。两个基因共有15种突变组合与环丙沙星耐药（MIC ≥ 3.13 μg/ml）相关，共193株（56.1%）。两种基因均含有突变的菌株对环丙沙星具有高度耐药性（50%分离株被抑制的MIC [MIC 50] = 50 μg/ml）。grlA中Ser-80→Phe或Tyr突变而gyrA为野生型的菌株对环丙沙星的耐药性较低（MIC 50 ≤ 12.5 μg/ml）。左氧氟沙星对193株grlA基因第80位密码子突变的分离株中的68株（35.2%）有活性，同时存在或不存在gyrA基因第73、84或88位密码子突变（MIC ≤ 6.25 μg/ml）。新氟喹诺酮DU-6859 a对193株分离株的MIC ≤6.25 μg/ml的有186株（96.4%）表现出良好的抗菌活性。
ABSTRACT Mutations in the grlA and gyrA genes of 344 clinical strains of Staphylococcus aureus isolated in 1994 in Japan were identified by combinations of single-strand conformation polymorphism analysis, restriction fragment length analysis, and direct sequencing to identify possible relationships to fluoroquinolone resistance. Five types of single-point mutations and four types of double mutations were observed in the grlA genes of 204 strains (59.3%). Four types of single-point mutations and four types of double mutations were found in the gyrA genes of 188 strains (54.7%). Among them, the grlA mutation of TCC→TTC or TAC (Ser-80→Phe or Tyr) and the gyrAmutation of TCA→TTA (Ser-84→Leu) were principal, being detected in 137 (39.8%) and 121 (35.9%) isolates, respectively. ThegrlA point mutations of CAT→CAC (His-77 [silent]), TCA→CCA (Ser-81→Pro), and ATA→ATT (Ile-100 [silent]) were novel, as was the GAC→GGC (Asp-73→Gly) change in gyrA. A total of 15 types of mutation combinations within both genes were related to ciprofloxacin resistance (MIC ≥ 3.13 μg/ml) and were present in 193 mutants (56.1%). Strains containing mutations in both genes were highly resistant to ciprofloxacin (MIC at which 50% of the isolates are inhibited [MIC50] = 50 μg/ml). Those with the Ser-80→Phe or Tyr alteration in grlA but wild-typegyrA showed a lower level of ciprofloxacin resistance (MIC50 ≤ 12.5 μg/ml). Levofloxacin was active against 68 of 193 isolates (35.2%) with mutations at codon 80 of grlAin the presence or absence of a concomitant mutation at codon 73, 84, or 88 in gyrA (MIC ≤ 6.25 μg/ml). The new fluoroquinolone DU-6859a showed good activity with 186 of 193 isolates (96.4%) for which the MIC was ≤6.25 μg/ml.