Identification of the varR gene as a transcriptional regulator of virginiamycin S resistance in Streptomyces virginiae

A gene designated varR (for virginiae antibiotic resistance regulator) was identified in Streptomyces virginiae 89 bp downstream of a varS gene encodi ng a virginiamycin S (VS)-specific transporter. The deduced varR product sh owed high homology to repressors of the TetR family with a conserved helix- turn-helix DNA binding motif. Purified recombinant VarR protein was present as a dimer in vitro and showed clear DNA binding activity toward the varS promoter region. This binding was abolished by the presence of VS, suggesti ng that VarR regulates transcription of varS in a VS-dependent manner. Nort hern blot analysis revealed that varR was cotranscribed with upstream varS as a 2.4-kb transcript and that VS acted as an inducer of bicistronic trans cription. Deletion analysis of the varS promoter region clarified two adjac ent VarR binding sites in the varS promoter.