Abstract

Mersacidin is a lanthionine-containing peptide antibiotic (lantibiotic), able to inhibit the growth of a number of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) in a manner similar to, but distinct from, vancomycin. In order to further understand the mode of action of this lantibiotic, Staphylococcus simulans 22 cells were treated either with the antibiotics penicillin, tunicamycin or vancomycin or with mersacidin and then compared with untreated cells after electron microscopic examination. Mersacidin treatment brought about a time-dependent, generalised decrease in the thickness of the bacterial cell wall. In addition, mersacidin treatment caused a roughening of the cell wall surface layer and also reduced the thickness and frequency of formation of dividing cell septa. Reduction of cell wall thickness appears to result from inhibition of new wall biosynthesis combined with cell wall turnover. These features of mersacidin-induced effects on cell morphology confirm that it has a novel mode of action ( Brötz, H., G. Bierbaum, A. Markus, E. Molitor, and H.-G. Sahl: Antimicrob. Agents Chemother. 39 [1995] 714-719), probably directed towards a membrane-bound biosynthetic step but not towards a specific penicillin-binding-protein.

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