Specific drug-sensing systems that coordinate appropriate genetic responses 
assure the survival of microorganisms in the presence of antibiotics. We report 
on the development and application of a microtiter plate-based bioassay for the 
identification of antibiotics interfering with the lipid II cycle essential for 
peptidoglycan biosynthesis. A Bacillus subtilis reporter strain sensing 
specifically lipid II - interfering cell wall biosynthesis stress (T. Mascher, 
S.L. Zimmer, T.-A. Smith and J. Helmann, Antibiotic-inducible promoter regulated 
by the cell envelope stress-sensing two-component system LiaRS of Bacillus 
subtilis; Antimicrob. Agents Chemother., Vol 48 (2004) pp. 2888-2896) was 
analyzed in the presence of different lantibiotics. We could show dose-dependent 
cell wall biosynthesis stress of reporter cells in response to the action of the 
lantibiotics subtilin produced by B. subtilis, epidermin and gallidermin of 
Staphylococcus epidermidis or S. gallinarum, respectively, in both, agar-plate 
and liquid culture-based assays. Surprisingly, also cinnamycin of Streptomyces 
cinnamoneus cinnamoneus), previously known to bind specifically to 
phosphatidylethanolamin of biological membranes, provoked strong cell wall 
biosynthetic stress. Our results show that our system can be used for screening 
purposes, for example to discover novel inhibitors of cell wall biosynthesis.