Multimeric assembly and dynamics of pore-forming lantibiotic peptide Nisin.

Abstract

Multidrug resistance in bacteria has led to a dire need for the development of new antibiotics with novel modes of action which can evade existing bacterial defenses. By targeting Lipid-II, antibiotic peptides such as Nisin disrupt bacteria's ability to synthesize their cell wall. Lantibiotics bind to Lipid-II's pyrophosphate moiety rather than the more commonly targeted peptide moiety. This means that bacteria that develop resistance to commercial antibiotics should still be vulnerable to lantibiotics. In this study, we use atomic-scale molecular dynamics computational studies to model stable oligomeric pore structures of Nisin and investigate their dynamics and stability. We test a variety of conformations of Nisin pore structures and motifs to find a viable structure. We also explore the role that Lipid-II plays in the formation and in maintaining the stability of the pores as well as the role transmembrane potentials play in the nature of the pores, including the channel volume and the ability of Nisin pores to exhibit ion selectivity.