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.
Klyachko
K A
KA
Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois 60607, USA.
Neyfakh
A A
AA
D000167:Acriflavine / Q000378:metabolism; D019943:Amino Acid Substitution; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004996:Ethidium / Q000378:metabolism; D019143:Evolution, Molecular; D026901:Membrane Transport Proteins; D009643:Norfloxacin / Q000378:metabolism; D011392:Proline / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D013753:Tetracycline Resistance
D001426:Bacterial Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D012097:Repressor Proteins; C107173:TetC protein, Bacteria; C075041:Bmr protein, Bacillus subtilis; D000167:Acriflavine; D011392:Proline; D004996:Ethidium; D009643:Norfloxacin