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Antimicrobial Agents and Chemotherapy, May 2005, p. 1915-1926, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1915-1926.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Global Transcriptional Response of Bacillus subtilis to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis

Janine T. Lin,* Mariah Bindel Connelly, Chris Amolo, Suzie Otani, and Debbie S. Yaver

Novozymes, Inc., 1445 Drew Ave., Davis, California 95616

Received 6 April 2004/ Returned for modification 11 July 2004/ Accepted 29 December 2004

Global gene expression patterns of Bacillus subtilis in response to subinhibitory concentrations of protein synthesis inhibitors (chloramphenicol, erythromycin, and gentamicin) were studied by DNA microarray analysis. B. subtilis cultures were treated with subinhibitory concentrations of protein synthesis inhibitors for 5, 15, 30, and 60 min, and transcriptional patterns were measured throughout the time course. Three major classes of genes were affected by the protein synthesis inhibitors: genes encoding transport/binding proteins, genes involved in protein synthesis, and genes involved in the metabolism of carbohydrates and related molecules. Similar expression patterns for a few classes of genes were observed due to treatment with chloramphenicol (0.4x MIC) or erythromycin (0.5x MIC), whereas expression patterns of gentamicin-treated cells were distinct. Expression of genes involved in metabolism of amino acids was altered by treatment with chloramphenicol and erythromycin but not by treatment with gentamicin. Heat shock genes were induced by gentamicin but repressed by chloramphenicol. Other genes induced by the protein synthesis inhibitors included the yheIH operon encoding ABC transporter-like proteins, with similarity to multidrug efflux proteins, and the ysbAB operon encoding homologs of LrgAB that function to inhibit cell wall cleavage (murein hydrolase activity) and convey penicillin tolerance in Staphylococcus aureus.

* Corresponding author. Mailing address: Novozymes, Inc., 1445 Drew Ave., Davis, CA 95616. Phone: (530) 757-4706. Fax: (530) 758-0317. E-mail: JLin{at}novozymes.com.

Antimicrobial Agents and Chemotherapy, May 2005, p. 1915-1926, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1915-1926.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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