title: Two highly similar multidrug transporters of Bacillus subtilis whose expression is differentially regulated.
abstract: The Bacillus subtilis genome encodes two multidrug efflux transporters sharing 51% sequence identity: Bmr, described previously, and Blt, described here. Overexpression of either transporter in B. subtilis leads to a similar increase in resistance to ethidium bromide, rhodamine and acridine dyes, tetraphenylphosphonium, doxorubicin, and fluoroquinolone antibiotics. However, Blt differs widely from Bmr in its expression pattern. Under standard cultivation conditions, B. subtilis expresses Bmr but Blt expression is undetectable. We have previously shown that Bmr expression is regulated by BmrR, a member of the family of MerR-like transcriptional activators. Here we show that blt transcription is regulated by another member of the same family, BltR. The DNA-binding domains of BmrR and BltR are related, but their putative inducer-binding domains are dissimilar, suggesting that Bmr and Blt are expressed in response to different inducers. Indeed, rhodamine, a substrate of Bmr and Blt and a known inducer of Bmr expression, does not induce Blt expression. Blt expression has been observed only in B. subtilis, carrying mutation acfA, which, as we show here, alters the sequence of the blt gene promoter. Unlike bmr, which is transcribed as a monocistronic mRNA, blt is cotranscribed with a downstream gene encoding a putative acetyltransferase. Overall, the differences in transcriptional control and operon organization between bmr and blt suggest that the transporters encoded by these genes have independent functions involving the transport of distinct physiological compounds.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago 60612, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ahmed
authors.forename: L
authors.initials: L
authors.lastname: Lyass
authors.forename: P N
authors.initials: PN
authors.lastname: Markham
authors.forename: S S
authors.initials: SS
authors.lastname: Taylor
authors.forename: N
authors.initials: N
authors.lastname: Vázquez-Laslop
authors.forename: A A
authors.initials: AA
authors.lastname: Neyfakh
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C093353:AcfA protein, Vibrio cholerae; D001426:Bacterial Proteins; C094576:BltR protein, Bacillus subtilis; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D015534:Trans-Activators; C075041:Bmr protein, Bacillus subtilis; C094575:Blt protein, Bacillus subtilis; D000123:Acetyltransferases; C094574:BltD protein, Bacillus subtilis