MDFA, AN ESCHERICHIA-COLI MULTIDRUG-RESISTANCE PROTEIN WITH AN EXTRAORDINARILY BROAD-SPECTRUM OF DRUG RECOGNITION

Multidrug resistance (MDR) translocators recently identified in bacter ia constitute an excellent model system for studying the MDR phenomeno n 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 resi dues which belongs to the major facilitator superfamily of transport p roteins, Cells expressing MdfA from a multicopy plasmid are substantia lly more resistant to a diverse group of cationic or zwitterionic lipo philic compounds such as ethidium bromide, tetraphenylphosphonium, rho damine, daunomycin, benzalkonium, rifampin, tetracycline, and puromyci n. Surprisingly, however, MdfA also confers resistance to chemically u nrelated, clinically important antibiotics such as chloramphenicol, er ythromycin, and certain aminoglycosides and fluoroquinolones. Transpor t experiments with an E. coli strain lacking F-1-F-0 proton ATPase act ivity indicate that MdfA is a multidrug transporter that is driven by the proton electrochemical gradient.