Zbl. Bakt. 284, 318-328 (1996) © Gustav Fischer Verlag, Stuttgart· Jena . New York Effects of the Lantibiotic Mersacidin on the Morphology of Staphylococci * E. MOLITOR, C. KLUCZNY, H. BROTZ, G. BIERBAUM, R. JACK, and H.-G. SAHL Institut fur Medizinische Mikrobiologie und Immunologie der Universitat Bonn, Germany Received March 13, 1996 . Accepted March 25,1996 Abstract Mersacidin is a lanthionine-containing peptide antibiotic (lantibiotic), able to inhibit the growth of a number of Gram-positive bacteria including methicillin-resistant Staphylococ- cus aureus (MRSA) in a manner similar to, but distinct from, vancomycin. In order to fur- ther understand the mode of action of this lantibiotic, Staphylococcus simulans 22 cells were treated either with the antibiotics penicillin, tunicamycin or vancomycin or with mer- sacidin and then compared with untreated cells after electron microscopic examination. Mersacidin treatment brought about a time-dependent, generalised decrease in the thick- ness 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 divid- ing 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 (Brotz, 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-bin ding-protein. Introduction Mersacidin is an antibacterial peptide with activity against a number of Gram-po- sitive bacteria such as various bacilli, streptococci and staphylococci, including strains of Staphylococcus aureus that are resistant to methicillin (so-called MRSA's; 7). In ani- mal models, mersacidin has been shown to be of therapeutic value in experimentally induced septicaemia and subcutaneous abscesses caused by S. aureus (17). Moreover, mersacidin activity seems to compare favourably with that of the glycopeptide antibio- tic vancomycin (7). The mersacidin peptide is a lantibiotic (24) produced by Bacillus sp. HIL Y- 85,54728 (8); in contrast to other peptide antibiotics from Bacillus sp. (15,20), mer- 'f Dedicated to Prof. Dr. H. Brandis on the occasion of his 80 th birthday.