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MTA: A global regulator of Bacillus subtilis multidrug transporters

Posted on:2001-11-11Degree:Ph.DType:Thesis
University:University of Illinois at Chicago, Health Sciences CenterCandidate:Baranova, Natalya NFull Text:PDF
GTID:2463390014457272Subject:Biology
Abstract/Summary:
The expression of two highly similar multidrug transporters of Bacillus subtilis, Bmr and Blt, is controlled by two independent mechanisms. Specific activators BmrR and MR, which respond to different inducer molecules, regulate transcription of the bmr and blt genes, respectively. An alternative mechanism of regulation, described here, involves a global transcriptional activator Mta, and allows simultaneous activation of both transporter genes in a response to an as yet unidentified stimulus. Mta is a member of the MerR family of bacterial regulatory proteins. The individually expressed amino 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 two more genes, ydfK and ywnC, both of which encode hypothetical membrane proteins. These results 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 carboxy-terminal inducer-binding domain.; mta mRNA can direct synthesis of two polypeptides---of the full-length Mta and of its carboxy terminal domain expressed independently. The latter is apparently synthesized as a result of the initiation of translation at an alternative site. Although such phenomenon is rarely observed in prokaryotes, synthesis of multiple polypeptides due to utilization of alternative initiatory codons has also been described for two other MerR-type proteins---TipA of Streptomyces lividans and NolA of Bradyrhizobium japonicum. It has been proposed that amino-terminally truncated versions of these proteins, which retain a ligand binding ability, but do not bind DNA, serve to sequester molecules of inducer and to prevent an uncontrollable amplification of response. Expression of the carboxy terminal domain of Mta can serve a similar function.; Mta is not expressed in Bacillus subtilis cells during vegetative growth and sporulation. It was also found not to be expressed under a variety of stress conditions. Deletion of the mta genes does not produce any easily discernible specific phenotype. Thus, role of the Mta protein in the cell remains enigmatic and requires further investigation.; The multiplicity of mechanisms controlling expression of multidrug transporters in Bacillus subtilis suggests that the bacterial cell takes advantage of the broad substrate specificity of each multidrug transporter and uses it for the transport of different substrates, depending on the physiological necessity.
Keywords/Search Tags:Bacillus subtilis, Multidrug, Mta, Global, Expression
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