Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na(+) or K(+). Inhibited by CCCP. Optimum pH is 6.5. Monomer. A negative charge at position 26 is required for efficient transport of positively charged substrates, but not for neutral compounds. This negative charge does not play an essential role in the multidrug transport mechanism. Has a sensitive conformational switch that can be triggered either by substrate binding or by attaching unrelated agents inside the pocket. Dissimilar substrates induce similar conformational changes. Belongs to the major facilitator superfamily. MdfA family.