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Antimicrobial Agents and Chemotherapy, March 2003, p. 948-955, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.948-955.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Proteomic Approach to Understanding Antibiotic Action

Julia Elisabeth Bandow,1,{dagger} Heike Brötz,2 Lars Ingo Ole Leichert,1 Harald Labischinski,2* and Michael Hecker1

Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität, 17489 Greifswald,1 Bayer AG, Pharmaforschungszentrum, 42096 Wuppertal, Germany2

Received 23 July 2002/ Returned for modification 25 October 2002/ Accepted 21 November 2002

We have used proteomic technology to elucidate the complex cellular responses of Bacillus subtilis to antimicrobial compounds belonging to classical and emerging antibiotic classes. We established on two-dimensional gels a comprehensive database of cytoplasmic proteins with pIs covering a range of 4 to 7 that were synthesized during treatment with antibiotics or agents known to cause generalized cell damage. Although each antibiotic showed an individual protein expression profile, overlaps in the expression of marker proteins reflected similarities in molecular drug mechanisms, suggesting that novel compounds with unknown mechanisms of action may be classified. Indeed, one such substance, a structurally novel protein synthesis inhibitor (BAY 50-2369), could be classified as a peptidyltransferase inhibitor. These results suggest that this technique gives new insights into the bacterial response toward classical antibiotics and hints at modes of action of novel compounds. Such a method should prove useful in the process of antibiotic drug discovery.

* Corresponding author. Mailing address: Bayer AG, Pharmaforschungszentrum, Postfach 10 17 09, 42096 Wuppertal, Germany. Phone: 49 (202) 368376. Fax: 49 (202) 364116. E-mail: harald.labischinski.hl{at}bayer-ag.de.

{dagger} Present address: Pfizer Inc., Ann Arbor, MI 48105.

Antimicrobial Agents and Chemotherapy, March 2003, p. 948-955, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.948-955.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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