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Journal of Bacteriology, May 1999, p. 3293-3297, Vol. 181, No. 10
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification and In Vivo Functional Analysis of a Virginiamycin S Resistance Gene (varS) from Streptomyces virginiae

Chang-Kwon Lee, Yuka Kamitani, Takuya Nihira,* and Yasuhiro Yamada

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

Received 9 November 1998/Accepted 8 March 1999

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.


* Corresponding author. Mailing address: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-7433. Fax: 81-6-6879-7432. E-mail: nihira{at}biochem.bio.eng.osaka-u.ac.jp.


Journal of Bacteriology, May 1999, p. 3293-3297, Vol. 181, No. 10
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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