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Journal of Bacteriology, June 2009, p. 3763-3771, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.00241-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Inhibition of Transcription in Staphylococcus aureus by a Primary Sigma Factor-Binding Polypeptide from Phage G1{triangledown}

Mohammed Dehbi,1* Gregory Moeck,1 Francis F. Arhin,1 Pascale Bauda,1 Dominique Bergeron,1 Tony Kwan,1 Jing Liu,1 John McCarty,1 Michael DuBow,2 and Jerry Pelletier3

Targanta Therapeutics, Saint Laurent, Canada H4S 2A1,1 Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay, France,2 Department of Biochemistry, McGill University, Montreal, Canada H3G 1Y63

Received 23 February 2009/ Accepted 7 April 2009

The primary sigma factor of Staphylococcus aureus, {sigma}SA, regulates the transcription of many genes, including several essential genes, in this bacterium via specific recognition of exponential growth phase promoters. In this study, we report the existence of a novel staphylococcal phage G1-derived growth inhibitory polypeptide, referred to as G1ORF67, that interacts with {sigma}SA both in vivo and in vitro and regulates its activity. Delineation of the minimal domain of {sigma}SA that is required for its interaction with G1ORF67 as amino acids 294 to 360 near the carboxy terminus suggests that the G1 phage-encoded anti-{sigma} factor may occlude the –35 element recognition domain of {sigma}SA. As would be predicted by this hypothesis, the G1ORF67 polypeptide abolished both RNA polymerase core-dependent binding of {sigma}SA to DNA and {sigma}SA-dependent transcription in vitro. While G1ORF67 profoundly inhibits transcription when expressed in S. aureus cells in mode of action studies, our finding that G1ORF67 was unable to inhibit transcription when expressed in Escherichia coli concurs with its inability to inhibit transcription by the E. coli holoenzyme in vitro. These features demonstrate the selectivity of G1ORF67 for S. aureus RNA polymerase. We predict that G1ORF67 is one of the central polypeptides in the phage G1 strategy to appropriate host RNA polymerase and redirect it to phage reproduction.

* Corresponding author. Present address: King Faisal Specialist Hospital and Research Centre, Dept. of Comparative Medicine MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Phone: 966 1 464-7272, ext. 32955. Fax: 966 1 442-7872. E-mail: mdehbi{at}kfshrc.edu.sa

{triangledown} Published ahead of print on 17 April 2009.

Journal of Bacteriology, June 2009, p. 3763-3771, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.00241-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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