Paradoxical enhancement of the activity of a bacterial multidrug transporter caused by substitutions of a conserved residue

Substitution of threonine or serine for the evolutionary conserved intramembrane proline P³⁴⁷ of the Bacillus subtilis multidrug transporter Bmr significantly increases the toxin-effluxing activity of Bmr without affecting its abundance in the cell. In cocultivation experiments, we demonstrate that although the mutant T³⁴⁷ Bmr is advantageous to cells growing in the presence of a toxin, the wild-type P³⁴⁷ Bmr is advantageous under the conditions of nutritional limitation. This may explain why Bmr has evolved the way it did, that is, with proline at position 347. These observations provide a basis for speculating that the evolution of Bmr has been determined by its presently unidentified natural function rather than by its ability to expel diverse toxins from the cell.