Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters.
Little is known about the natural functions of multidrug-efflux transporters expressed by bacteria. Although identified as membrane proteins actively extruding exogenous toxins from the cell, they may actually be involved in the transport of as yet unidentified specific natural substrates. The expression of two highly similar multidrug transporters of Bacillus subtilis, Bmr and Blt, is regulated by specific transcriptional activators, BmrR and BltR, respectively, which respond to different inducer molecules, thus suggesting distinct functions for the two transporters. Here, we describe an alternative mechanism of regulation, which involves a global transcriptional activator, Mta, a member of the MerR family of bacterial regulatory proteins. The individually expressed N-terminal DNA-binding domain of Mta interacts directly with the promoters of bmr and blt and induces transcription of these genes. Additionally, this domain stimulates the expression of the mta gene itself and at least one more gene, ydfK, which encodes a hypothetical membrane protein. These results and the similarity of Mta to the thiostrepton-induced protein TipA of Streptomyces lividans strongly suggest that Mta is an autogenously controlled global transcriptional regulator, whose activity is stimulated by an as yet unidentified inducer. This stimulation is mimicked by the removal of the C-terminal inducer-binding domain. The fact that both Bmr and Blt are controlled by this regulator demonstrates that some of their functions are either identical or, at least, related. Further analysis of Mta-mediated regulation may reveal the natural function of the system of multidrug transporters in B. subtilis and serve as a paradigm for similar systems in other bacteria.
Baranova
N N
NN
Center for Pharmaceutical Biotechnology (M/C 870), University of Illinois, Chicago 60607, USA.
Danchin
A
A
Neyfakh
A A
AA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000123:Acetyltransferases; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D018983:DNA Footprinting; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D005838:Genotype; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013883:Thiostrepton / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D014161:Transduction, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C094576:BltR protein, Bacillus subtilis; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C051124:MerR protein, Bacteria; C119773:Mta protein, Bacillus subtilis; D015534:Trans-Activators; C075041:Bmr protein, Bacillus subtilis; C094575:Blt protein, Bacillus subtilis; D000123:Acetyltransferases; C094574:BltD protein, Bacillus subtilis; D013883:Thiostrepton