Abstract
BarA of Streptomyces virginiae is a specific receptor protein for virginiae butanolide (VB), one of the gamma-butyrolactone autoregulators of the Streptomyces species, and acts as a transcriptional regulator controlling both virginiamycin production and VB biosynthesis. The downstream gene barB, the transcription of which is under the tight control of the VB-BarA system, was found to be transcribed as a polycistronic mRNA with its downstream region, and DNA sequencing revealed a 1,554-bp open reading frame (ORF) beginning at 161 bp downstream of the barB termination codon. The ORF product showed high homology (68 to 73%) to drug efflux proteins having 14 transmembrane segments and was named varS (for S. virginiae antibiotic resistance). Heterologous expression of varS with S. lividans as a host resulted in virginiamycin S-specific resistance, suggesting that varS encoded a virginiamycin S-specific transport protein. Northern blot analysis indicated that the bicistronic transcript of barB-varS appeared 1 to 2 h before the onset of virginiamycin M1 and S production, at which time VB was produced, while exogenously added virginiamycin S apparently induced the monocistronic varS transcript.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives
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4-Butyrolactone / biosynthesis
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Amino Acid Sequence
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Anti-Bacterial Agents / biosynthesis
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology*
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics*
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Bacterial Proteins / metabolism
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Base Sequence
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Biological Transport
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Blotting, Northern
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Drug Resistance, Microbial / genetics*
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Gene Expression Regulation, Bacterial / drug effects
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Genes / genetics
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Genes, Bacterial
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Open Reading Frames / genetics
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Promoter Regions, Genetic / genetics
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Streptomyces / drug effects*
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Streptomyces / genetics
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Streptomyces / metabolism
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Time Factors
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Transformation, Bacterial
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Virginiamycin / biosynthesis
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Virginiamycin / metabolism
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Virginiamycin / pharmacology*
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Membrane Proteins
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RNA, Messenger
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Recombinant Proteins
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varS protein, Streptomyces virginiae
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Virginiamycin
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4-Butyrolactone