Alterations in the DNA topoisomerase IV responsible for quinolone resistance in MRSA and MRSE

我们试图确定表皮葡萄球菌和金黄色葡萄球菌临床分离株的gyrA和parC基因的部分序列，并试图评估gyrA和parC基因突变与MRSA和MRSE中氟喹诺酮耐药的相关性。gyrA基因的决定区和parC基因的类似区。65株大肠埃希菌parC基因第80位丝氨酸（Ser 80）的改变与喹诺酮类药物耐药有关。此外，parC和gyrA突变的顺序获得导致更高水平的抗性。这些数据有力地表明，ParC突变以及GyrA突变也是MRSA对氟喹诺酮类药物耐药的重要因素。我们检测了7株耐氟喹诺酮类药物的MRSE突变株的gyrA和parC基因突变。5株突变株ParC基因发生单氨基酸变异，2株高水平氟喹诺酮耐药株GyrA基因发生双氨基酸变异（Ser 84-Try & Asp 94-Gly）和ParC中的单个氨基酸变化。表皮葡萄球菌（包括MRSE）中喹诺酮耐药性的最重要因素似乎是靶酶如DNA促旋酶和DNA拓扑异构酶IV的突变，以及由于降低的药物渗透和/或增加的药物流出而导致降低的药物积累的突变。

We tried to determine partial sequences of the gyrA and parC genes of clinical isolates of Staphylococcus epidermidis and Staphylococcus aureus and attempted to assess the association of mutations in the gyrA and parC genes with fluoroquinolone resistance in MRSA and MRSE Sequence analysis of PCR products from 65 fluoroquinolone-resistant clinical isolates of MRSA was used to examine the quinolone resistance-determining regions of the gyrA gene and the analogous regions of the parC gene. The changes of the serine at position 80 (Ser 80) in parC of 65 strains ested were associated with resistance to quinolone antibacterials. Moreover, sequential acquisition of mutations in parC and gyrA led to higher levels of resistance. These data strongly suggest that ParC mutations as well as GyrA mutations are also important factor for fluoroquinolone resistance in MRSA.Seven fluoroquinolone-resistant mutants of MRSE were examined for mutations in the gyrA and parC genes. While five mutants had a single amino acid changes in ParC,two higher level fluoroquinolone-resistant isolates had a double amino acid change in GyrA (Ser84-Try & Asp94-Gly) and a single amino acid change in ParC.The most important factor for quinolone resistance in S.epidermidis including MRSE seems to be the mutations of target enzymes such as DNA gyrase and DNA topoisomerase IV,and mutations causing decreased drug accumulation due to decreased drug penetration and/or increased drug efflux.