细菌多重耐药泵的研究进展  

Multidrug Efflux Systems Involved in Resistance to Antibacterial Drugs

作　　者：王春梅[1] 何启盖[1] 操继跃[2] 

机构地区：[1]华中农业大学农业微生物学国家重点实验室,武汉430070 [2]华中农业大学动物医学院,武汉430070

出　　处：《畜牧兽医学报》2011年第4期455-467,共13页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：国家生猪产业技术体系(nycytx-009)

摘　　要：细菌主要通过药物代谢酶将药物失活、靶向改造药物作用部位、降低细胞膜通透性和通过耐药泵主动将胞内药物泵出胞外4种方式抵抗抗生素和其他药物的毒性作用,其中细菌通过耐药泵将药物排出胞外是细菌的主要耐药机制之一,尤其是多重耐药泵,可以外排结构迥异的多种药物或对细菌有毒的代谢产物。由于细胞膜结构的不同,革兰氏阴性菌和革兰氏阳性菌所具有的耐药泵种类和结构也有所不同。革兰氏阴性菌中,目前发现的细菌耐药泵种类主要包括ATP结合盒超家族(ATP-binding cassette family,ABC)、耐药节结化细胞分化(resistancenodulation division,RND)家族、主要易化子超家族(major facilitator superfamily,MFS)、小多重耐药(small multi-drug resistance,SMR)家族和多药及毒性化合物外排家族(multidrug and toxic-compound extrusion family,MA-TE)。革兰氏阳性菌中,目前发现的细菌耐药泵种类主要包括ABC、MFS、SMR和MATE家族。近年来,诸多学者开展了细菌耐药泵的结构及其耐药机制的研究,并且已有新药研发团队以绿脓杆菌耐药泵MexAB-OprM的结构为作用靶点开发新的抗菌药物做了大量的探索工作,天然化合物和常规药物中也存在能够抑制耐药泵活性的化合物。作者主要针对耐药泵的分类、不同细菌中耐药泵的特征及耐药泵作为新药作用靶点的潜在应用价值进行综述。Bacteria have developed various ways to resist the toxic effects of antibiotics and other drugs,such as produce enzymes that inactivate antibiotics,target alteration by mutation or enzymatic modification,inhibit drug entry into the cell and active efflux of drugs.Actively exporting an antibiotic from the bacterial cell by the efflux pump is essential to ensure significant levels of drug resistance.The multidrug efflux pumps that affect such efflux typically export several unrelated substances,including antibiotics and molecules produced by the host organism.There are different kinds of multidrug efflux pumps in gram-negative bacteria and that in gram-positive bacteria as the different structure of cell membrane.In gram-negative bacteria,it has been reported five superfamilies,which include ATP-binding cassette family（ABC）,resistance nodulation division（RND） family,major facilitator superfamily（MFS）,small multidrug resistanc（SMR） family and multidrug and toxic-compound extrusion family（MATE）.In gram-positive bacteria,it has been reported four superfamilies,which include ABC,MFS,SMR and MATE family,except RND family.Facing the resistance of bacteria to antibiotics,it is urgent to find new molecules mechanisms against resistant bacteria.Some researchers have been searching for the efflux pumps inhibitors（e.g.,MexAB-OprM specific efflux pump inhibitor） for several years,and some possible compounds have been identified from medicinal plant to restore antibiotic activity.

关 键 词：细菌 多重耐药泵 耐药泵抑制剂 

分 类 号：Q756[生物学—分子生物学] S852.61[农业科学—基础兽医学]