Efflux of the natural polyamine spermidine facilitated by the Bacillus subtilis multidrug transporter Blt.
Multidrug transporters pump structurally dissimilar toxic molecules out of cells. It is not known, however, if detoxification is the primary physiological function of these transporters. The chromosomal organization of the gene encoding the Bacillus subtilis multidrug transporter Blt suggests a specific function for this protein; it forms a single operon with another gene, bltD, whose protein product is identified here as a spermine/spermidine acetyltransferase, an enzyme catalyzing a key step in spermidine degradation. Overexpression of the Blt transporter in B. subtilis leads not only to the multidrug-resistance phenotype but also to the efflux of large amounts of spermidine into the medium; this efflux is supressed by an inhibitor of Blt, reserpine. Taken together, these results strongly suggest that the natural function of the Blt transporter is the efflux of spermidine, whereas multiple drugs may be recognized by Blt merely opportunistically.
Woolridge
D P
DP
Departments of Biochemistry and Radiation Oncology, The University of Arizona Health Science Center, Tucson, Arizona 85724, USA.
Vazquez-Laslop
N
N
Markham
P N
PN
Chevalier
M S
MS
Gerner
E W
EW
Neyfakh
A A
AA
D000107:Acetylation; D000123:Acetyltransferases; D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D026901:Membrane Transport Proteins; D009876:Operon; D012110:Reserpine / Q000494:pharmacology; D013095:Spermidine / Q000378:metabolism*; D013565:Sympatholytics / Q000494:pharmacology; D015534:Trans-Activators
D001426:Bacterial Proteins; C094576:BltR protein, Bacillus subtilis; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D013565:Sympatholytics; D015534:Trans-Activators; C094575:Blt protein, Bacillus subtilis; D012110:Reserpine; D000123:Acetyltransferases; C094574:BltD protein, Bacillus subtilis; D013095:Spermidine