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Journal of Bacteriology, December 2004, p. 8407-8423, Vol. 186, No. 24
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.24.8407-8423.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effect of Mild Acid on Gene Expression in Staphylococcus aureus

Brian Weinrick,1 Paul M. Dunman,2,{dagger} Fionnuala McAleese,2 Ellen Murphy,2 Steven J. Projan,2 Yuan Fang,1 and Richard P. Novick1*

Molecular Pathogenesis Program, Skirball Institute, and Department of Microbiology, New York University Medical Center, New York,1 Wyeth Research, Pearl River, New York2

Received 29 July 2004/ Accepted 15 September 2004

During staphylococcal growth in glucose-supplemented medium, the pH of a culture starting near neutrality typically decreases by about 2 units due to the fermentation of glucose. Many species can comfortably tolerate the resulting mildly acidic conditions (pH, ~5.5) by mounting a cellular response, which serves to defend the intracellular pH and, in principle, to modify gene expression for optimal performance in a mildly acidic infection site. In this report, we show that changes in staphylococcal gene expression formerly thought to represent a glucose effect are largely the result of declining pH. We examine the cellular response to mild acid by microarray analysis and define the affected gene set as the mild acid stimulon. Many of the genes encoding extracellular virulence factors are affected, as are genes involved in regulation of virulence factor gene expression, transport of sugars and peptides, intermediary metabolism, and pH homeostasis. Key results are verified by gene fusion and Northern blot hybridization analyses. The results point to, but do not define, possible regulatory pathways by which the organism senses and responds to a pH stimulus.

* Corresponding author. Mailing address: Program in Molecular Pathogenesis, Skirball Institute, and Department of Microbiology, New York University School of Medicine, 540 First Ave., New York, NY 10016. Phone: (212) 263-6290. Fax: (212) 263-5711. E-mail: novick{at}saturn.med.nyu.edu.

{dagger} Present address: University of Nebraska Medical Center, Omaha, NE 68198-6495.

Journal of Bacteriology, December 2004, p. 8407-8423, Vol. 186, No. 24
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.24.8407-8423.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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