Margolles Abelardo, Flórez Ana Belén, Moreno José Antonio, van Sinderen Douwe, de Los Reyes-Gavilán Clara G
Instituto de Productos Lácteos de Asturias, Consejo Superior de Investigaciones Científicas (CSIC), Ctra Infiesto s/n, 33300, Villaviciosa, Asturias, Spain.
Department of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Western Road, Cork, Ireland.
Microbiology (Reading). 2006 Dec;152(Pt 12):3497-3505. doi: 10.1099/mic.0.29097-0.
Intrinsic resistance to drugs is one of the main determining factors in bacterial survival in the intestinal ecosystem. This is mediated by, among others, multidrug resistance (MDR) transporters, membrane proteins which extrude noxious compounds with very different chemical structures and cellular targets. Two genes from Bifidobacterium breve encoding hypothetical membrane proteins with a high homology with members of the ATP-binding cassette (ABC) family of multidrug efflux transporters, were expressed separately and jointly in Lactococcus lactis. Cells co-expressing both proteins exhibited enhanced resistance levels to the antimicrobials nisin and polymyxin B. Furthermore, the drug extrusion activity in membrane vesicles was increased when both proteins were co-expressed, compared to membranes in which the proteins were produced independently. Both proteins were co-purified from the membrane as a stable complex in a 1:1 ratio. This is believed to be the first study of a functional ABC-type multidrug transporter in Bifidobacterium and contributes to our understanding of the molecular mechanisms underlying the capacity of intestinal bacteria to tolerate cytotoxic compounds.
对药物的内在抗性是肠道生态系统中细菌存活的主要决定因素之一。这尤其由多药抗性（MDR）转运蛋白介导，这些膜蛋白能排出具有非常不同化学结构和细胞靶点的有害化合物。来自短双歧杆菌的两个基因编码与ATP结合盒（ABC）家族多药外排转运蛋白成员具有高度同源性的假定膜蛋白，它们分别和共同在乳酸乳球菌中表达。共表达这两种蛋白的细胞对乳链菌肽和多粘菌素B的抗菌抗性水平增强。此外，与独立表达这两种蛋白的膜相比，当两种蛋白共表达时，膜囊泡中的药物外排活性增加。两种蛋白以1:1的比例作为稳定复合物从膜中共同纯化出来。据信这是对双歧杆菌中功能性ABC型多药转运蛋白的首次研究，有助于我们理解肠道细菌耐受细胞毒性化合物能力背后的分子机制。
