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 int ramembrane proline p(347) of the Bacillus subtilis multidrug transport er Bmr significantly increases the toxin-effluxing activity of Bmr wit hout affecting its abundance in the cell. In cocultivation experiments , we demonstrate that although the mutant T-347 Bmr is advantageous to cells growing in the presence of a toxin, the wild-type P-347 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 p osition 347, These observations provide a basis for speculating that t he evolution of Bmr has been determined by its presently unidentified natural function rather than by its ability to expel diverse toxins fr om the cell.