美国北卡罗来纳大学科研人员发现了金黄色葡萄球菌（Staphylococcus aureus）是如何向其他细菌传播多种药物耐药性的。
金黄色葡萄球菌的感染已经变得越来越难以治疗，因为出现的菌株能耐受诸如甲氧西林和万古霉素等强有力的抗生素。
美国北卡罗来纳大学教堂山分校化学系的Matthew Redinbo及其同事瞄准了称为葡萄球菌切口酶（NES）的一种细菌酶，并且揭示了它在细菌之间输送耐药性的中心作用。此前的研究已经证明了耐药性可以通过质粒在细菌之间转移，质粒是有别于细菌染色体的小型环状细菌DNA。现在证实了这种转移依赖于葡萄球菌切口酶（NES）。
这组作者揭示出了这种酶的氨基酸链的称为N和C端结构域的两个主要区域的晶体结构，此外还揭示出了表明整个酶与细菌DNA结合的结构。这些发现揭示出这种酶的N和C端结构域结合起来启动了质粒向非耐药细菌细胞的输送，转移一旦完成，这种结合就会终止这个过程。这组作者使用这种晶体结构作为指导，设计出了一种合成聚合物，它针对细菌DNA的小沟从而抑制葡萄球菌切口酶（NES）。
作者表示，这种合成聚合物可能有助于指导未来的研究，从而开发出针对对大多数抗生素有耐受性的金黄色葡萄球菌菌株的有效疗法。
Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.
Jonathan S. Edwards, Laurie Betts, Monica L. Frazier, Rebecca M. Polleta, Stephen M. Kwong, William G. Walton, W. Keith Ballentine III, Julianne J. Huang, Sohrab Habibi, Mark Del Campo, Jordan L. Meier, Peter. B. Dervane, Neville Firth, and Matthew R. Redinbo
Abstract：Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase.
文献链接：Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus.
