MUTATIONS AFFECTING SUBSTRATE-SPECIFICITY OF THE BACILLUS-SUBTILIS MULTIDRUG TRANSPORTER BMR

The Bacillus subtilis multidrug transporter Bmr, a member of the major facilitator superfamily of transporters, causes the efflux of a numbe r of structurally unrelated toxic compounds from cells. We have shown previously that the activity of Bmr can be inhibited by the plant alka loid reserpine. Here we demonstrate that various substitutions of resi dues Phe(143) and phe(306) Of Bmr not only reduce its sensitivity to r eserpine inhibition but also significantly change its substrate specif icity. Cross-resistance profiles of bacteria expressing mutant forms o f the transporter differ from each other and from the cross-resistance profile of cells expressing wild-type Emr. This result strongly sugge sts that Bmr interacts with its transported drugs directly, with resid ues Phe(143) and Phe(306) likely to be involved in substrate recogniti on.