细菌多重耐药泵的研究进展

被引:13
作者
王春梅 [1 ]
何启盖 [1 ]
操继跃 [2 ]
机构
[1] 华中农业大学农业微生物学国家重点实验室
[2] 华中农业大学动物医学院
关键词
细菌; 多重耐药泵; 耐药泵抑制剂;
D O I
暂无
中图分类号
S852.61 [病原细菌];
学科分类号
090601 ;
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。
引用
收藏
页码:455 / 467
页数:13
相关论文
共 13 条
[1]  
Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii : resistance mechanisms and implications for therapy[J] . Zavascki,Carvalhaes,Pic?o,Gales.Expert Review of Anti-infective Therapy . 2010 (1)
[2]  
Environmental-mediated drug resistance: a target for multiple myeloma therapy[J] . Shain,Dalton.Expert Review of Hematology . 2009 (6)
[3]   Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group [J].
Samosorn, Siritron ;
Tanwirat, Bongkot ;
Muhamad, Nussara ;
Casadei, Gabriele ;
Tomkiewicz, Danuta ;
Lewis, Kim ;
Suksamrarn, Apichart ;
Prammananan, Therdsak ;
Gornall, Karina C. ;
Beck, Jennifer L. ;
Bremner, John B. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (11) :3866-3872
[4]  
Resistance to tetracycline, erythromycin and clindamycin in Streptococcus suis serotype 2 in Hong Kong[J] . Yiu Wai Chu,Terence K.M. Cheung,Man Yu Chu,Vivien Y.M. Tsang,John T.L. Fung,Kai Man Kam,Janice Y.C. Lo.International Journal of Antimicrobial Agents . 2009 (2)
[5]   Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors [J].
Nargotra, Amit ;
Sharma, Sujata ;
Koul, Jawahir Lal ;
Sangwan, Pyare Lal ;
Khan, Inshad Ali ;
Kumar, Ashwani ;
Taneja, Subhash Chander ;
Koul, Surrinder .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (10) :4128-4135
[6]  
MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa . Part 7: Highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate[J] . Ken-ichi Yoshida,Kiyoshi Nakayama,Masami Ohtsuka,Noriko Kuru,Yoshihiro Yokomizo,Atsunobu Sakamoto,Makoto Takemura,Kazuki Hoshino,Hiroko Kanda,Hironobu Nitanai,Kenji Namba,Kumi Yoshida,Yuichiro Imamura,Jason Z. Zhang,Ving J. Lee,William J. Watkins.Bioorganic & Medicinal Chemistry . 2007 (22)
[7]  
Pseudomonas aeruginosa : resistance and therapeutic options at the turn of the new millennium[J] . N. Mesaros,P. Nordmann,P. Plésiat,M. Roussel-Delvallez,J. Van Eldere,Y. Glupczynski,Y. Van Laethem,F. Jacobs,P. Lebecque,A. Malfroot,P.M. Tulkens,F. Van Bambeke.Clinical Microbiology and Infection . 2007 (6)
[8]  
MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa . Part 6: Exploration of aromatic substituents[J] . Ken-ichi Yoshida,Kiyoshi Nakayama,Yoshihiro Yokomizo,Masami Ohtsuka,Makoto Takemura,Kazuki Hoshino,Hiroko Kanda,Kenji Namba,Hironobu Nitanai,Jason Z. Zhang,Ving J. Lee,William J. Watkins.Bioorganic & Medicinal Chemistry . 2006 (24)
[9]   Practical applications and feasibility of efflux pump inhibitors in the clinic - A vision for applied use [J].
Lomovskaya, O ;
Bostian, KA .
BIOCHEMICAL PHARMACOLOGY, 2006, 71 (07) :910-918
[10]  
The relationship between physicochemical properties, In vitro activity and pharmacokinetic profiles of analogues of diamine-Containing efflux pump inhibitors[J] . William J. Watkins,Yakira Landaverry,Roger Léger,Renée Litman,Thomas E. Renau,Nicole Williams,Rose Yen,Jason Z. Zhang,Suzanne Chamberland,Deidre Madsen,David Griffith,Vrushali Tembe,Keith Huie,Michael N. Dudley.Bioorganic & Medicinal Chemistry Letters . 2003 (23)