H1 helix of colicin U causes phospholipid membrane permeation

0552507 - ÚFCH JH 2023 RIV NL eng J - Journal Article
Riedlová, Kamila - Dolejšová, T. - Fišer, R. - Cwiklik, Lukasz
H1 helix of colicin U causes phospholipid membrane permeation.
Biochimica Et Biophysica Acta-Biomembranes. Roč. 1864, č. 4 (2022), č. článku 183866. ISSN 0005-2736. E-ISSN 1879-2642
R&D Projects: GA ČR(CZ) GA18-26751S
Institutional support: RVO:61388955
Keywords : Colicins * Leakage * Lipid membranes * Molecular dynamics * Permeation * Poration
OECD category: Physical chemistry
Impact factor: 3.4, year: 2022
Method of publishing: Limited access

In light of an increasing number of antibiotic-resistant bacterial strains, it is essential to understand an action imposed by various antimicrobial agents on bacteria at the molecular level. One of the leading mechanisms of killing bacteria is related to the alteration of their plasmatic membrane. We study bio-inspired peptides originating from natural antimicrobial proteins colicins, which can disrupt membranes of bacterial cells. Namely, we focus on the α-helix H1 of colicin U, produced by bacterium Shigella boydii, and compare it with analogous peptides derived from two different colicins. To address the behavior of the peptides in biological membranes, we employ a combination of molecular simulations and experiments. We use molecular dynamics simulations to show that all three peptides are stable in model zwitterionic and negatively charged phospholipid membranes. At the molecular level, their embedment leads to the formation of membrane defects, membrane permeation for water, and, for negatively charged lipids, membrane poration. These effects are caused by the presence of polar moieties in the considered peptides. Importantly, simulations demonstrate that even monomeric H1 peptides can form toroidal pores. At the macroscopic level, we employ experimental co-sedimentation and fluorescence leakage assays. We show that the H1 peptide of colicin U incorporates into phospholipid vesicles and disrupts their membranes, causing leakage, in agreement with the molecular simulations. These insights obtained for model systems seem important for understanding the mechanisms of antimicrobial action of natural bacteriocins and for future exploration of small bio-inspired peptides able to disrupt bacterial membranes.
Permanent Link: http://hdl.handle.net/11104/0327618