title: Lipid-II Independent Antimicrobial Mechanism of Nisin Depends On Its Crowding And Degree Of Oligomerization.
abstract: Nisin inhibits bacterial growth by generating pores in cell membrane and interrupting cell-wall biosynthesis through specific lipid II interaction. However, the role of the hinge region and C-terminus residues of the peptide in antibacterial action of nisin is largely unknown. Here, using molecular dynamics simulations and experimental approach, we report that at high concentration regimes of nisin, interaction with phospholipids may equally deform the bacterial cell membranes even under significantly varying amounts of lipid-II. Membrane thinning, destabilization and decrease in lipid density depend on the degree of oligomerization of nisin. Growth kinetics of Bacillus subtilis and Escherichia coli interestingly show recovery by extended lag phase under low concentrations of nisin treatment while high concentrations of nisin caused decrease in cell viability as recorded by striking reduction in membrane potential and surface area. The significant changes in the dipole potential and fluorescence anisotropy were observed in negatively charged membranes in the absence of lipid-II with increasing concentration of nisin. The identical correlation of cell viability, membrane potential dissipation and morphology with the concentration regime of nisin, in both Bacillus subtilis (lipid II rich) and Escherichia coli (lipid II impoverished), hints at a non-specific physical mechanism where degree of membrane deformation depends on degree of crowding and oligomerization of nisin.
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Prince
authors.affiliation: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, India.
authors.forename: Padmani
authors.initials: P
authors.lastname: Sandhu
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Ror
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Eva
authors.initials: E
authors.lastname: Dash
authors.affiliation: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, India.
authors.forename: Shingarika
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Arakha
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Jha
authors.affiliation: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, India.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Akhter
authors.affiliation: Department of Life Sciences, National Institute of Technology, Rourkela, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Saleem
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008051:Lipid Bilayers; D008055:Lipids / Q000737:chemistry*; D008564:Membrane Potentials / Q000187:drug effects; D056004:Molecular Dynamics Simulation; D009561:Nisin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008055:Lipids; D009561:Nisin