Mta, a global MerR-type regulator of the Bacillus subtilis multidrug-efflux transporters

Little is known about the natural functions of multidrug-efflux transporter s 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 expre ssion of two highly similar multidrug transporters of Bacillus subtilis, Bm r and Fit, is regulated by specific transcriptional activators, BmrR and Bl tR, respectively, which respond to different inducer molecules, thus sugges ting distinct functions for the two transporters. Here, we describe an alte rnative mechanism of regulation, which involves a global transcriptional ac tivator, 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 bit and induces transcription of the se genes. Additionally, this domain stimulates the expression of the mta ge ne itself and at least one more gene, ydfK, which encodes a hypothetical me mbrane 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 activit y is stimulated by an as yet unidentified inducer, This stimulation is mimi cked by the removal of the C-terminal inducer-binding domain. The fact that both Bmr and Bit are controlled by this regulator demonstrates that some o f their functions are either identical or, at least, related. Further analy sis of Mta-mediated regulation may reveal the natural function of the syste m of multidrug transporters in B. subtilis and serve as a paradigm for simi lar systems in other bacteria.