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伯克霍尔德氏菌 1026b 的 BpeAB-OprB 外排泵在群体感应、毒力因子产生或氨基糖苷类药物外排中不起作用,但它是一种广谱药物外排系统。

The BpeAB-OprB efflux pump of Burkholderia pseudomallei 1026b does not play a role in quorum sensing, virulence factor production, or extrusion of aminoglycosides but is a broad-spectrum drug efflux system.

机构信息

Department of Microbiology, Immunology and Pathology, Colorado State University, IDRC at Foothills Campus, Campus Delivery 2025, Fort Collins, CO 80523-2025, USA.

出版信息

Antimicrob Agents Chemother. 2010 Aug;54(8):3113-20. doi: 10.1128/AAC.01803-09. Epub 2010 May 24.

Abstract

Most Burkholderia pseudomallei strains are intrinsically aminoglycoside resistant, mainly due to AmrAB-OprA-mediated efflux. Rare naturally occurring or genetically engineered mutants lacking this pump are aminoglycoside susceptible despite the fact that they also encode and express BpeAB-OprB, which was reported to mediate efflux of aminoglycosides in the Singapore strain KHW. To reassess the role of BpeAB-OprB in B. pseudomallei aminoglycoside resistance, we used mutants overexpressing or lacking this pump in either AmrAB-OprA-proficient or -deficient strain 1026b backgrounds. Our data show that BpeAB-OprB does not mediate efflux of aminoglycosides but is a multidrug efflux system which extrudes macrolides, fluoroquinolones, tetracyclines, acriflavine, and, to a lesser extent, chloramphenicol. Phylogenetically, BpeAB-OprB is closely related to Pseudomonas aeruginosa MexAB-OprM, which has a similar substrate spectrum. AmrAB-OprA is most closely related to MexXY, the only P. aeruginosa efflux pump known to extrude aminoglycosides. Since BpeAB-OprB in strain KHW was also implicated in playing a major role in export of acylated homoserine lactone (AHL) quorum-sensing molecules and in expression of diverse virulence factors, we explored whether this was also true in the strain 1026b background. The results showed that BpeAB-OprB was not required for AHL export, and mutants lacking this efflux system exhibited normal swimming motility and siderophore production, which were severely impaired in KHW bpeAB-oprB mutants. Biofilm formation was impaired in 1026b Delta(amrRAB-oprA) and Delta(amrRAB-oprA) Delta(bpeAB-oprB) mutants. At present, we do not know why our BpeAB-OprB susceptibility and virulence factor expression results with 1026b and its derivatives are different from those previously published for Singapore strain KHW.

摘要

大多数伯克霍尔德氏菌(Burkholderia pseudomallei)菌株本质上对氨基糖苷类药物具有抗性,主要是由于 AmrAB-OprA 介导的外排作用。尽管罕见的天然或基因工程突变体缺乏这种泵,但它们也编码和表达 BpeAB-OprB,据报道该泵在新加坡菌株 KHW 中介导氨基糖苷类药物的外排,但它们对氨基糖苷类药物仍具有敏感性。为了重新评估 BpeAB-OprB 在伯克霍尔德氏菌(Burkholderia pseudomallei)氨基糖苷类药物抗性中的作用,我们使用在 AmrAB-OprA 功能齐全或缺失的 1026b 菌株背景下过度表达或缺乏该泵的突变体进行了研究。我们的数据表明,BpeAB-OprB 不介导氨基糖苷类药物的外排,但它是一种多药物外排系统,可排出大环内酯类、氟喹诺酮类、四环素类、吖啶黄素,并且在较小程度上还排出氯霉素。从系统发育上看,BpeAB-OprB 与铜绿假单胞菌(Pseudomonas aeruginosa)MexAB-OprM 密切相关,后者具有相似的底物谱。AmrAB-OprA 与 MexXY 最为密切相关,MexXY 是已知唯一能排出氨基糖苷类药物的铜绿假单胞菌(Pseudomonas aeruginosa)外排泵。由于 KHW 菌株中的 BpeAB-OprB 也被认为在酰化高丝氨酸内酯(AHL)群体感应分子的出口和多种毒力因子的表达中起主要作用,因此我们探讨了在 1026b 菌株背景下是否也是如此。结果表明,BpeAB-OprB 不参与 AHL 外排,缺乏该外排系统的突变体表现出正常的泳动能力和铁载体产生能力,而在 KHW bpeAB-oprB 突变体中,这些能力严重受损。生物膜形成在 1026b Delta(amrRAB-oprA) 和 1026b Delta(amrRAB-oprA) Delta(bpeAB-oprB) 突变体中受到损害。目前,我们尚不清楚为什么我们在 1026b 及其衍生物中进行的 BpeAB-OprB 药敏性和毒力因子表达结果与之前针对新加坡菌株 KHW 发表的结果不同。

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