Mersacidin is an antibiotic peptide produced by Bacillus sp. strain HIL 
Y-85,54728 that belongs to the group of lantibiotics. Its activity in vivo 
against methicillin-resistant Staphylococcus aureus strains compares with that 
of the glycopeptide antibiotic vancomycin (S. Chatterjee, D. K. Chatterjee, R. 
H. Jani, J. Blumbach, B. N. Ganguli, N. Klesel, M. Limbert, and G. Seibert, J. 
Antibiot. 45:839-845, 1992). Incubation of Staphylococcus simulans 22 with 
mersacidin resulted in the cessation of growth and slow lysis. Biosyntheses of 
DNA, RNA, and protein were not affected, whereas incorporation of glucose and 
D-alanine was inhibited and a regular reduction in the level of cell wall 
thickness was observed. Thus, unlike type A lantibiotics, mersacidin does not 
form pores in the cytoplasmic membrane but rather inhibits cell wall 
biosynthesis. Comparison with tunicamycin-treated cells indicated that 
peptidoglycan rather than teichoic acid metabolism is primarily affected. 
Mersacidin caused the excretion of a putative cell wall precursor into the 
culture supernatant. The formation of polymeric peptidoglycan was effectively 
inhibited in an in vitro assay, probably on the level of transglycosylation. In 
contrast to vancomycin, the activity of mersacidin was not antagonized by the 
tripeptide diacetyl-L-Lys-D-Ala-D-Ala, indicating that on the molecular level 
its mode of action differs from those of glycopeptide antibiotics. These data 
together with electron microscopy suggest that mersacidin acts on a novel 
target, which opens new perspectives for the treatment of methicillin-resistant 
S. aureus.