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Mode of Action of MCB3681 in Staphylococcus aureus a Proteomic Study

Birgit Voigt, Dirk Albrecht and Axel Dalhoff

Background: MCB3681, a novel quinolonyl-oxazolidinone antibacterial, is active against quinolone- and/or linezolidresistant Gram-positive bacteria. Thus, MCB3681 may interact with other targets than quinolones and oxazolidinones.

Methods and Findings: Protein expression in S. aureus following short-term exposure to MCB3681 was analyzed using 2D-gel electrophoresis and MALDI-TOF-MS/MS. Synthesis of 13 and 16 proteins was induced or repressed, respectively. Among the induced proteins are four ribosomal proteins. Repressed are proteins from different amino acid synthesis pathways, two aminoacyl-tRNAsynthetases, and methicillin-resistance-factor-protein FemB.

Conclusion: Our findings demonstrate that the impact of MCB3681 on the proteome signature of treated S. aureus cells is different from that of either ciprofloxacin or linezolid.