摘要

降低目标亲和力或减少药物积累的突变导致革兰氏阴性病原体中大多数喹诺酮耐药性增加，但不解释抗性发展的迅速程度或其与其他抗微生物剂抗性的频繁联系。质粒介导的喹诺酮抗性（PMQR）的三种机制，长期以来认为不会发生，自1998年以来已被发现。质粒基因qnrA，qnrB，qnrC，qnrD，qnrS和qnrVC编码五肽重复家族蛋白质，其保护DNA促旋酶和来自喹诺酮抑制的拓扑异构酶IV。qnr基因似乎是从水生细菌中获得的，通常与质粒中的动员或转座元件相关联，并且通常被并入sul1型整合子中。第二种PMQR机制涉及通过常见氨基糖苷乙酰转移酶AAC（6'）-Ib的变体乙酰化某些喹诺酮。第三种机制是泵QepAB和OqxAB质粒基因产生的外排增强。质粒介导的机制仅提供低水平的抗性，其本身不超过易感性的临床断点，但仍有助于选择更高水平的抗性并使含有PMQR基因的病原体更难以治疗。

Mutations that reduce target affinity or decrease drug accumulation are responsible for most of the increased quinolone resistance in gram-negative pathogens but do not account for how rapidly resistance has developed or its frequent linkage to resistance to other antimicrobial agents. Three mechanisms for plasmid-mediated quinolone resistance (PMQR), long thought not to occur, have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protect DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from aquatic bacteria, are usually associated on plasmids with mobilizing or transposable elements, and are often incorporated into sul1-type integrons. The second PMQR mechanism involves acetylation of certain quinolones by a variant of the common aminoglycoside acetyltransferase AAC(6′)-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher level resistance and makes pathogens containing PMQR genes harder to treat.

https://link.springer.com/chapter/10.1007%2F978-3-319-46718-4_17