Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients
Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients
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DOI：
10.1111/j.1469-0691.2008.02097.x
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发表时间：
2009-01-01
影响因子：
14.2
通讯作者：
Wretlind, B.
中科院分区：
文献类型：
--
作者：
Islam, S.;Oh, H.;Wretlind, B.
本研究共纳入40株来自囊性纤维化（CF）患者的铜绿假单胞菌分离株。其中20个是在1994年和1997年从6名CF患者中收集的，其余的是在2000年和2001年从不同的CF患者中收集的。通过实时PCR测定外排泵蛋白MexY mRNA的相对表达，并与阿米卡星和妥布霉素的敏感性相关。分析了染色体基因mexZ、rplY、galU、PA 5471和nuoG，这些基因被发现在铜绿假单胞菌的实验室突变体中对氨基糖苷类抗生素的MIC逐渐增加具有作用。在1994年和1997年收集的20株分离株中，有17株发现MexY mRNA过度表达，并且与对氨基糖苷类药物敏感性降低相关。MexXY-OprM外排系统的改变是3年期间CF铜绿假单胞菌分离株对氨基糖苷类抗生素耐药的主要机制。在一些分离株中，PA 5471基因产物的表达可能对氨基糖苷类药物的MIC升高有一定影响。rplY、galU和/或nuoG的失活可以解释氨基糖苷类在实验室突变体中MIC的逐渐增加，但可能不是在CF环境中，因为rplY和galU在所有分离株中均未改变，并且nuoG仅在一个分离株中不表达。在13个被调查的分离株中，没有发现16 S rRNA A位点突变的基因的四个拷贝中的任何一个。
In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux pump protein MexY was determined by real-time PCR and correlated with susceptibilities to amikacin and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which were found to have a role in the gradual increase in MICs of aminoglycoside antibiotics in laboratory mutants of P. aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P. aeruginosa isolates over the 3-year period. In several isolates, expression of the PA5471 gene product might have some effect on elevated MICs of aminoglycosides. Inactivation of rplY, galU and/or nuoG may explain the gradual increase in MICs of aminoglycosides in laboratory mutants but probably not in the CF environment, as rplY and galU were unaltered in all isolates, and nuoG was not expressed in only one isolate. No 16S rRNA A-site mutations were found in any of the four copies of the gene in 13 investigated isolates.