The lantibiotic mersacidin has been previously reported to interfere with 
bacterial peptidoglycan biosynthesis, [Brötz, H., Bierbaum, G., Markus, A., 
Molitor, E. & Sahl, H.-G. (1995) Antimicrob. Agents Chemother. 39, 714-719]. 
Here, we focus on the target reaction and describe a mersacidin-induced 
accumulation of UDP-N-acetylmuramoyl-pentapeptide, indicating that inhibition of 
peptidoglycan synthesis occurs after the formation of cytoplasmic precursors. In 
vitro studies involving a wall-membrane particulate fraction of Bacillus 
megaterium KM demonstrated that mersacidin did not prevent the synthesis of 
lipid II [undecaprenyl-diphosphoryl-N-acetylmuramoyl-(pentapeptide)-N-ac ety 
lglucosamine] but specifically the subsequent conversion of this intermediate 
into polymeric nascent glycan strands by transglycosylation. Comparison with 
other inhibitors of transglycosylation shows that the effective concentration of 
mersacidin in vitro is in the range of that of the glycopeptide antibiotic 
vancomycin but 2-3 orders of magnitude higher than that of the competitive 
enzyme inhibitor moenomycin. The analogy to the glycopeptides may hint at an 
interaction of mersacidin with the peptidoglycan precursor rather than with the 
enzyme. Unlike vancomycin however, mersacidin inhibits peptidoglycan formation 
from UDP-N-acetylmuramoyl-tripeptide and is active against Enterococcus faecium 
expressing the vanA resistance gene cluster. This indicates that the molecular 
target site of mersacidin differs from that of vancomycin and that no 
cross-resistance exists between the two antibiotics.