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Journal of Bacteriology, September 2005, p. 5893-5900, Vol. 187, No. 17
0021-9193/05/$08.00+0     doi:10.1128/JB.187.17.5893-5900.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A LysR-Type Regulator, CidR, Is Required for Induction of the Staphylococcus aureus cidABC Operon

Soo-Jin Yang,1 Kelly C. Rice,1 Raquel J. Brown,1 Toni G. Patton,1 Linda E. Liou,1 Yong Ho Park,2 and Kenneth W. Bayles1*

Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho 83844-3052,1 College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea2

Received 28 April 2005/ Accepted 13 June 2005

The Staphylococcus aureus cidABC and lrgAB operons have been shown to regulate murein hydrolase activity and affect antibiotic tolerance. The cid operon enhances murein hydrolase activity and antibiotic sensitivity, whereas the lrg operon inhibits these processes. Based on these findings and the structural similarities of the cidA and lrgA gene products to the bacteriophage holin family of proteins, we have proposed that the cid and lrg operons encode holin- and antiholin-like proteins, respectively, that function to control the murein hydrolase activity produced by the bacteria. Analysis of cid operon transcription revealed the presence of two transcripts, one spanning all three cid genes and whose expression is induced by growth in the presence of acetic acid and the other spanning cidB and cidC only that is produced in a sigma B-dependent manner. The cidABC operon lies immediately downstream from the cidR gene, encoding a potential LysR-type transcriptional regulator. In this study, we demonstrate that cidR is involved in the regulation of cidABC expression. Northern blot analyses revealed that the cidR gene product positively regulates cidABC expression by increasing transcription in the presence of acetic acid produced as a result of the metabolism of glucose. As expected for an operon that encodes a positive effector of murein hydrolase activity, the upregulation of cidABC expression resulted in increased murein hydrolase activity produced by these cells. Furthermore, it was demonstrated that antibiotic tolerance and stationary-phase survival of S. aureus are affected by the cidR gene. Taken together, these results demonstrate that the cidR gene product functions as a transcriptional activator of cidABC transcription in response to acetic acid accumulation in the growth medium.

* Corresponding author. Present address: Department of Pathology and Microbiology, University of Nebraska Medical Center, 668 S. 41st St., PYH4014, Omaha, NE 68105-6245. Phone: (402) 559-4945. Fax: (402) 559-4070. E-mail: kbayles{at}unmc.edu.

Journal of Bacteriology, September 2005, p. 5893-5900, Vol. 187, No. 17
0021-9193/05/$08.00+0     doi:10.1128/JB.187.17.5893-5900.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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