肠杆菌科质粒介导喹诺酮类抗菌药耐药的研究

Plasmid-mediated resistance to quinolones in Enterobacteriaceae

肠杆菌中喹诺酮类抗菌药耐药大多是由染色体突变引起的,但也可能由含Qnr基因的质粒介导。Qnr蛋白保护DNA不受喹诺酮类药物的影响而降低敏感性,如萘啶酸。Qnr蛋白包括QnrA蛋白、QnrB蛋白和QnrS蛋白,在亚洲广泛存在于被克拉维酸抑制的超广谱β-内酰胺酶和质粒介导的头孢菌素酶的肠杆菌科中,并快速蔓延。QnrA基因包含在su l1型整合子中。近年来,在水生的海藻谢瓦纳拉菌中发现了与QnrA基因起源非常接近的基因,提示液体环境可能决定了QnrA基因在体内的转移场所。进一步分析这种基因转移的作用,可能对阻止这种耐药性在肠杆菌科细菌中的蔓延具有一定指导意义,并可能引出一种新的抗菌药物耐药机制。

Although quinolone resistance results mostly from chromosomal mutations in Enterobacteriaceae, it may also be mediated by plasmid-encoded Qnr determinants. Qnr proteins protect DNA from quinolone action and compromise the effect of quinolones, such as nalidixic acid. Qnr proteins including QnrA, QnrB and QnrS, have been identified worldwide with a quite high prevalence among Asian isolates with a frequent association with clavulanic acid-inhibited expanded-spectrum b-lactamases and plasmid-mediated cephalosporinases. The QnrA genes are embedded in complex sull-type integrons. A close relative and likely progenitor of the QnrA have been found in the water-borne species Shewanella algae. It may help to determine the location of in vivo transfer of the QnrA genes. Further analyses of the role of quinolones, if any, in enhancing this gene transfer may prevent the spreading of the drug resistance and possibly lead to the finding of a novel mechanism of antibiotic resistance.