摘要
目的研究嗜麦芽窄食单胞菌DNA解旋酶和拓谱异构酶的突变与氟喹诺酮类药物(FQNS)的耐药关系,为新药开发提供实验依据。方法选择对环丙沙星最低抑菌浓度(MIC)≥2mg/L且主动外排表型机制阴性的菌株,对其gyrA和parE的喹诺酮决定区域基因分别进行PCR扩增,纯化后直接测序。结果嗜麦芽窄食单胞菌在DNA解旋酶最常见的83位和87位没有突变,同时在GyrA的整个喹诺酮耐药决定区域(QRDRs)没有氨基酸的改变,并且其83位是Gln而不是其它革兰阴性菌常见的Ser或Thr。5株菌中的parE各有1株菌在402和432突变,但是该突变与FQNS耐药不相关,未观察到Valdezate研究中的1/2菌株的parE突变频率高且主要集中在437、465、477和485位的现象。结论嗜麦芽窄食单胞菌对FQNS耐药与主动外排泵有关,可能与外膜的通透性降低有关,但与DNA解旋酶和拓谱异构酶的靶位点改变关系尚不明确,需进一步研究。
Objective To research DNA gyrase and topoisomerase Ⅳ quinolone reslstance-determlnlng regions (QRDRs) in Stenotrophomonas maltophilia clinical isolates with different resistant levels of quinolone susceptibility. Methods We selected five strains for which the MIC of ciprofloxacin were higher than 2 mg/L and were negative for efflux mechanism ; then we amplified their QRDRs of gyrA and parE, purified the fragment, and analyzed the nucleotide sequences. Results In Stenotrophomonas maltophilia DNA gyrA, the changes at positions 83 and 87 commonly involved in quinolones resistance in gram-negatlve bacteria were absent, and there was Gln but not Ser or Thr. Of the five strains, one strain showed a Pare amino acid change in position 402, the other was in position 432, but the mutations were not associated with FQNS resistance. Conclusion FQNS resistance in Stenotrophomonas maltophilia is related to active efflux pump and may be correlated with a low level of permeability. But it is not clear whether the resistance is related to the mutants in DNA gyrase and topoisomerase Ⅳ.
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2006年第2期266-269,共4页
Journal of Sichuan University(Medical Sciences)