AcrA dependency of the AcrD efflux pump in Salmonella enterica serovar Typhimurium
AcrA dependency of the AcrD efflux pump in Salmonella enterica serovar Typhimurium
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DOI：
10.1038/ja.2011.28
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发表时间：
2011-06-01
影响因子：
3.3
通讯作者：
Nishino, Kunihiko
中科院分区：
文献类型：
--
作者：
Yamasaki, Seiji;Nagasawa, Saya;Nishino, Kunihiko
属于耐药-增殖细胞分裂（RND）家族的多药外排泵在革兰氏阴性菌对多种化合物的内在耐药性和耐药性升高中起主要作用。RND外排泵需要另外两种蛋白质才能发挥作用：膜融合蛋白（MFP）和外膜蛋白。最近的研究表明，沙门氏菌鼠伤寒血清型具有五种RND外排系统：AcrAB，AcrD，AcrEF，MdtABC和MdsABC。大多数RND外排系统基因也在同一操纵子中编码MFP;然而，MFP基因并不位于acrD附近，并且与AcrD起作用的MFP仍有待详细研究。本研究的目的是调查在这种生物体的AcrD外排系统的MFP的要求。当过量产生时，AcrD显著增加了acrB突变体对苯唑西林、氯唑西林、萘夫西林、羧苄西林、磺苄西林、氨曲南、十二烷基硫酸钠和新生霉素的抗性。通过删除MFP基因acrA或多功能外膜通道基因tolC，AcrD过量产生引起的耐药性增加被完全抑制。虽然acrD的过表达并没有赋予耐药性的三角洲acrAB株，acrA的acrD的共过表达增加了这种突变体的多药耐药性。我们的研究结果表明，AcrA MFP和TolC外膜蛋白，除了在AcrB外排系统中的作用外，还需要在S.鼠伤寒沙门氏菌The Journal of Antibiotics（2011）64，433-437; doi：10.1038/ja.2011.28; 2011年4月20日在线发表
Multidrug efflux pumps belonging to the resistance-nodulation cell division (RND) family have major roles in the intrinsic and elevated resistance of Gram-negative bacteria to a wide range of compounds. RND efflux pumps require two other proteins to function: a membrane fusion protein (MFP) and an outer membrane protein. A recent study demonstrated that Salmonella enterica serovar Typhimurium has five RND efflux systems: AcrAB, AcrD, AcrEF, MdtABC and MdsABC. Most RND efflux system genes also code for an MFP in the same operon; however, an MFP gene is not located near acrD, and the MFP, with which AcrD functions, remains to be studied in detail. The aim of this study was to investigate the requirement of an MFP for the AcrD efflux system in this organism. When overproduced, AcrD significantly increased the resistance of the acrB mutant to oxacillin, cloxacillin, nafcillin, carbenicillin, sulbenicillin, aztreonam, sodium dodecyl sulfate and novobiocin. The increase in drug resistance caused by AcrD overproduction was completely suppressed by deleting the MFP gene, acrA, or the multifunctional outer membrane channel gene, tolC. Although the overexpression of acrD did not confer drug resistance to the Delta acrAB strain, co-overexpression of acrD with acrA increased the multidrug resistance of this mutant. Our results indicate that the AcrA MFP and TolC outer membrane protein, in addition to their roles in the AcrB efflux system, are required for the function of the AcrD efflux pump in S. enterica serovar Typhimurium. The Journal of Antibiotics (2011) 64, 433-437; doi:10.1038/ja.2011.28; published online 20 April 2011