In bacterial membranes lipid II changes the stability of pores formed by the antimicrobial peptide nisin

Resistance to available antibiotics poses a growing challenge to modern medicine as this often disallows infections to be controlled. This problem can only be alleviated by developing new drugs. Nisin, a natural lantibiotic with broad antimicrobial activity, has shown promise as a potential candidate for combating antibiotic-resistant bacteria. However, nisin is poorly soluble and barely stable at physiological pH, which, despite attempts to address these issues through mutant design, has restricted its use as a antibacterial drug. Therefore, gaining a deeper understanding of the antimicrobial effectiveness, which relies in part on its ability to form pores, is crucial for finding innovative ways to manage infections caused by resistant bacteria. Using large-scale molecular dynamics simulations we find that the bacterial membrane specific lipid II increases the stability of pores formed by nisin, and that the interplay of nisin and lipid II reduces the overall integrity of bacterial membranes by changing local thickness and viscosity.