MdfA, an Escherichia coli multidrug resistance protein with an extraordinarily broad spectrum of drug recognition.
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 F1-F0 proton ATPase activity indicate that MdfA is a multidrug transporter that is driven by the proton electrochemical gradient.
Edgar
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Department of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
Bibi
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D001693:Biological Transport, Active; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000235:genetics*; D004996:Ethidium / Q000494:pharmacology; D005798:Genes, Bacterial; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D015183:Restriction Mapping; D016415:Sequence Alignment; D012995:Solubility; D013379:Substrate Specificity
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008565:Membrane Proteins; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D004996:Ethidium; C013289:tetraphenylphosphonium