Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City
Correlation of the expression of acrB and the regulatory genes marA, soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City
复制标题
DOI：
10.1093/jac/dkp186
复制
发表时间：
2009-08-01
影响因子：
5.2
通讯作者：
Quale, John
中科院分区：
文献类型：
--
作者：
Bratu, Simona;Landman, David;Quale, John
肺炎克雷伯菌医院分离株耐所有常用的抗菌药物已出现在世界许多地区。目前尚不清楚外排系统是否与多药耐药表型有关，我们检测了外排泵AcrAB和全局调节因子MarA、SoxS和拉马的基因表达，并将其与耐药性相关。几乎所有这些分离株的基因表达可忽略不计或不存在，对氟喹诺酮类和氨基糖苷类的耐药性可以通过替代机制来解释。所有这些分离株均对替加环素敏感。还检查了一组14个异质分离株。marA与soxS的表达存在相关性。只有soxS的表达与acrB的表达显著相关。随着GyrA背景替换，acrB和marA的表达增加似乎有助于一些分离株对氟喹诺酮类药物的耐药性。soxS和拉马的表达之间存在相关性在体外暴露于替加环素后，在缺乏soxS和拉马表达的分离株中，耐药性的发生与marA和acrB表达的显著增加相关。临床分离株中替加环素MIC的变化仅与选定的调节基因相关。似乎除了acrAB系统的激活之外，还有其他机制介导替加环素耐药性。
Nosocomial isolates of Klebsiella pneumoniae resistant to all commonly used antimicrobial agents have emerged in many regions of the world. It is unknown if efflux systems contribute to the multidrug resistance phenotype.The expression of genes encoding the efflux pump AcrAB and the global regulators MarA, SoxS and RamA were examined and correlated with antimicrobial resistance.Twenty isolates belonged to the two important clones representing KPC-possessing strains endemic to our region. Virtually all of these isolates had negligible or absent expression of the genes, and resistance to fluoroquinolones and aminoglycosides could be explained by alternative mechanisms. All of these isolates were susceptible to tigecycline. A group of 14 heterogeneous isolates was also examined. There was a correlation between expression of marA with expression of soxS. Only expression of soxS was significantly correlated with expression of acrB. With a background substitution in GyrA, increased expression of acrB and marA appeared to contribute to fluoroquinolone resistance in some isolates. A correlation was noted between expression of soxS and ramA (but not marA and acrB) and tigecycline MICs. Following in vitro exposure to tigecycline, resistance occurred in association with a marked increase in marA and acrB expression in isolates lacking expression of soxS and ramA.While laboratory-derived tigecycline resistance was associated with increased acrB expression, the variation in tigecycline MICs in clinical isolates was associated only with selected regulator genes. It appears that other mechanisms beyond activation of the acrAB system mediate tigecycline resistance.