Quinolone action in Escherichia coli cells carrying gyrA and gyrB mutations.
Quinolone action in Escherichia coli cells carrying gyrA and gyrB mutations.
复制标题
喹诺酮在携带 gyrA 和 gyrB 突变的大肠杆菌细胞中的作用。
作者：
G. Herrera;V. Aleixandra;A. Urios;M. Blanco
我们分离出大肠杆菌 KL16 的自发突变株，表现出不同水平的萘啶酸 (NAL) 抗性。在 40 个独立突变体中，36 个具有 gyrA 突变，4 个具有 gyrB 突变。大多数 gyrA 突变 (30/36) 赋予高水平的 NAL 抗性。相比之下，唯一赋予相对较高水平的 NAL 抗性的 gyrB 突变也决定了对喹诺酮环 C7 位置具有哌嗪基取代基的喹诺酮类药物（两性喹诺酮类药物）的敏感性增强。该gyrB突变（表示为gyrB1604）与赋予高水平喹诺酮抗性的gyrA突变（表示为gyrA972）一起用于构建携带两个gyr突变等位基因的菌株IC2476。该菌株对两性喹诺酮类药物（哌啶酸、诺氟沙星和环丙沙星）的敏感性与gyrA972单突变体相似。该结果表明，决定高水平喹诺酮抗性的GyrA亚基的变化能够掩盖由GyrB1604突变体亚基促进的对两性喹诺酮类药物的过度敏感性。通过研究环丙沙星 (CFX) 对 gyrA972 gyrB1604 菌株中促旋酶抑制的影响，进一步证实了这种能力。
We have isolated spontaneous mutant strains of Escherichia coli KL16 showing different levels of nalidixic acid (NAL) resistance. From 40 independent mutants, 36 had gyrA and four had gyrB mutations. Most of the gyrA mutations (30/36) conferred high level NAL resistance. In contrast, the only gyrB mutation that conferred a relatively high level of NAL resistance also determined enhanced susceptibility to quinolones with a piperazinyl substituent at C7 position of the quinolone ring (amphoteric quinolones). This gyrB mutation (denoted gyrB1604), jointly with a gyrA mutation (denoted gyrA972) which confers a high level of quinolone resistance, were used to construct strain IC2476, carrying the two gyr mutant alleles. The susceptibility of this strain to amphoteric quinolones (pipemidic acid, norfloxacin and ciprofloxacin) was similar to that of the gyrA972 single mutant. This result indicates that the change in GyrA subunit which determines a high level of quinolone-resistance has the capacity to mask the hypersusceptibility to amphoteric quinolones promoted by the GyrB1604 mutant subunit. This capacity was further confirmed by studying the effects of ciprofloxacin (CFX) on gyrase inhibition in the gyrA972 gyrB1604 strain.