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 number of structurally unrelated toxic compounds from cells. We have shown previously that the activity of Bmr can be inhibited by the plant alkaloid reserpine. Here we demonstrate that various substitutions of residues Phe(143) and phe(306) Of Bmr not only reduce its sensitivity to reserpine inhibition but also significantly change its substrate specificity. Cross-resistance profiles of bacteria expressing mutant forms of the transporter differ from each other and from the cross-resistance profile of cells expressing wild-type Emr. This result strongly suggests that Bmr interacts with its transported drugs directly, with residues Phe(143) and Phe(306) likely to be involved in substrate recognition.