Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity

To date, a number of lantibiotics have been shown to use lipid II-a highly conserved peptidoglycan precursor in the cytoplasmic membrane of bacteria-as their molecular target. The alpha-component (Lch alpha) of the two-component lantibiotic lichenicidin, previously isolated from the Bacillus licheniformis VK21 strain, seems to contain two putative lipid II binding sites in its N-terminal and C-terminal domains. Using NMR spectroscopy in DPC micelles, we obtained convincing evidence that the C-terminal mersacidin-like site is involved in the interaction with lipid II. These data were confirmed by the MD simulations. The contact area of lipid II includes pyrophosphate and disaccharide residues along with the first isoprene units of bactoprenol. MD also showed the potential for the formation of a stable N-terminal nisin-like complex; however, the conditions necessary for its implementation in vitro remain unknown. Overall, our results clarify the picture of two component lantibiotics mechanism of antimicrobial action.

Automated summary

To date, several lantibiotics have been found to target lipid II, a peptidoglycan precursor in bacterial cytoplasmic membrane. The alpha-component of lichenicidin, a two-component lantibiotic, contains potential lipid II binding sites. NMR spectroscopy and MD simulations provided evidence that the C-terminal domain of lichenicidin interacts with lipid II. The contact area of lipid II includes pyrophosphate, disaccharide residues, and bactoprenol's first isoprene units.