Proteomic approach to understanding antibiotic action.
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.
Bandow
Julia Elisabeth
JE
Institut für Mikrobiologie, Ernst-Moritz-Arndt-Universität, 17489 Greifswald, Germany.
Brötz
Heike
H
Leichert
Lars Ingo Ole
LI
Labischinski
Harald
H
Hecker
Michael
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000737:chemistry / Q000187:drug effects; D016172:DNA Fingerprinting; D004591:Electrophoresis, Polyacrylamide Gel; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D008715:Methionine / Q000378:metabolism; D009582:Nitrofurantoin / Q000494:pharmacology; D040901:Proteomics; D011744:Pyrimidinones / Q000494:pharmacology; D013462:Sulfur Radioisotopes
D000900:Anti-Bacterial Agents; D000892:Anti-Infective Agents, Urinary; C476337:BAY 50-2369; D001426:Bacterial Proteins; D011744:Pyrimidinones; D013462:Sulfur Radioisotopes; D009582:Nitrofurantoin; D008715:Methionine