MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition

MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition
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DOI:
10.1128/jb.179.7.2274-2280.1997
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发表时间:
1997-04-01
影响因子:
3.2
通讯作者:
Bibi, E
Bibi, E
中科院分区:
生物学3区
文献类型:
--
作者:
Edgar, R;Bibi, E

文献摘要

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最近在细菌中发现的多药耐药(MDR)转运子是研究MDR现象及其临床意义的一个很好的模型系统。本文报道了大肠杆菌中一个不寻常的MDR基因(mdfA)的鉴定和特性。mdfA编码一个410个氨基酸残基的膜蛋白(MdfA),属于转运蛋白的主要易化剂超家族,从多拷贝质粒表达MdfA的细胞对不同的阳离子或两性离子亲脂性化合物如溴化乙锭、四苯基磷、罗丹明、道诺霉素、苯扎溴铵、利福平、四环素和嘌呤霉素具有显著更高的抗性。然而,令人惊讶的是,MdfA也赋予对化学上不相关的、临床上重要的抗生素如氯霉素、红霉素和某些氨基糖苷类和氟喹诺酮类的抗性。用E.缺乏F-1-F-0质子ATP酶活性的大肠杆菌菌株表明,MdfA是一种由质子电化学梯度驱动的多药物转运蛋白。
Multidrug resistance (MDR) translocators recently identified in bacteria constitute an excellent model system for studying the MDR phenomenon and its clinical relevance, Here we describe the identification and characterization of an unusual MDR gene (mdfA) from Escherichia coli, mdfA encodes a putative membrane protein (MdfA) of 410 amino acid residues which belongs to the major facilitator superfamily of transport proteins, Cells expressing MdfA from a multicopy plasmid are substantially more resistant to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampin, tetracycline, and puromycin. Surprisingly, however, MdfA also confers resistance to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Transport experiments with an E. coli strain lacking F-1-F-0 proton ATPase activity indicate that MdfA is a multidrug transporter that is driven by the proton electrochemical gradient.