Two classes of ethidium-bromide-resistant mutants of Streptomyces lividans 66

Five spontaneous mutants of Streptomyces lividans TK64 resistant to 5 or 15 microM ethidium bromide (EB) were isolated, and the corresponding mutations were mapped to two different chromosomal locations. Both types of mutations conferred unselected resistance to several basic dyes and norfloxacin. The strain with the low-level resistance exhibited wild-type levels of EB uptake and energy-dependent efflux, and the resistance mechanism is unclear. The highly resistant mutants, which additionally were resistant to phosphonium ions, had a reduced accumulation and an increased efflux of EB, reminiscent of a mammalian multidrug resistance efflux pump.