Intramembrane Nanoaggregates of Antimicrobial Peptides Play a Vital Role in Bacterial Killing. Issue 3 (23rd November 2022)

• Record Type: Journal Article
• Authors: Liao, Mingrui; Gong, Haoning; Quan, Xuebo; Wang, Ziwei; Hu, Xuzhi; Chen, Zheng; Li, Zongyi; Liu, Huayang; Zhang, Lin; McBain, Andrew J.; Waigh, Thomas A.; Zhou, Jian; Lu, Jian Ren
• Is Part Of: Small. Volume 19:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-23
• Subjects: antimicrobial efficiency -- antimicrobial peptide design -- antimicrobial peptides -- bionanomaterials -- intramembrane aggregation -- lipid membranes -- nanoaggregates -- self‐assembly; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202204428
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Recent developments in antimicrobial peptides (AMPs) have focused on the rational design of short sequences with less than 20 amino acids due to their relatively low synthesis costs and ease of correlation of the structure‐function relationship. However, gaps remain in the understanding of how short cationic AMPs interact with the bacterial outer and inner membranes to affect their antimicrobial efficacy and dynamic killing. The membrane‐lytic actions of two designed AMPs, G(IIKK)3 I‐NH2 (G3 ) and G(IIKK)4 I‐NH2 (G4 ), and previously‐studied controls GLLDLLKLLLKAAG‐NH2 (LDKA, biomimetic) and GIGAVLKVLTTGLPALISWIKRKR‐NH2 (Melittin, natural) are examined. The mechanistic processes of membrane damage and the disruption strength of the four AMPs are characterized by molecular dynamics simulations and experimental measurements including neutron reflection and scattering. The results from the combined studies are characterized with distinctly different intramembrane nanoaggregates formed upon AMP‐specific binding, reflecting clear influences of AMP sequence, charge and the chemistry of the inner and outer membranes. G3 and G4 display different nanoaggregation with the outer and inner membranes, and the smaller sizes and further extent of insertion of the intramembrane nanoaggregates into bacterial membranes correlate well with their greater antimicrobial efficacy and faster dynamic killing. This work demonstrates the crucial roles of intramembrane nanoaggregates in optimizing antimicrobial efficacy and dynamic killing. Abstract : Antimicrobial peptides' actions on POPC/POPG (1‐palmitoyl‐2‐oleoyl‐glycero‐3‐phosphocholine; 1‐palmitoyl‐2‐oleoyl‐ sn ‐glycero‐3‐phospho‐(1′‐ rac ‐glycerol)) small unilamellar vesicles (SUVs) mimicking the inner membrane of Gram‐negative bacteria displaying different membrane disruptions.