Interaction of cationic antimicrobial peptides from Australian frogs with lipid membranes

Abstract

Cationic antimicrobial peptides (AMPs) from Australian frogs have been extensively studied as alternatives to traditional antibiotics. Solid‐state NMR is used to characterize their effect on lipid bilayers, which are the primary target, but correlation with in vivo situations is tentative in view of the complex effects of changes in sample conditions (such as pH, temperature, lipid composition or peptide concentration). We have used 31P and 2H solid‐state NMR and a range of biophysical techniques to study the impact of the AMPs, maculatin 1.1, caerin 1.1, aurein 1.2, kalata B1, and Chex‐Arg20, on membranes that mimic those of E. coli and S. aureus bacteria and red blood cell membranes. Overall, the length of AMPs affects peptide‐membrane interaction but also their conformations are important. While lipid composition plays a critical role in modulating AMP structure and function, electrostatic interactions are not sufficient to explain their specific activity and interactions with other membrane components need to be considered. Although in an early stage of development, in‐cell NMR of labelled peptides in live bacteria, rather than model membrane studies, may provide new insights into bactericidal mechanisms of AMPs.

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

“…As opposed to common AMPs, many CPPs are able to enter the cell without damaging the membrane [ 7 , 8 , 32 ] and exert their killing action inducing apoptosis or targeting intracellular macromolecules such as DNA, RNA, ribosomes or organelles such as mitochondria [ 11 , 31 , 109 , 125 , 126 , 127 , 128 ], as it is the case for MPPs [ 11 ]. This mechanism is used by CPPs such as coprisin, some magainins or cecropins and postulated for CXJ [ 4 , 5 ].…”

Antimicrobial Peptide K11 Selectively Recognizes Bacterial Biomimetic Membranes and Acts by Twisting Their Bilayers

“…As opposed to standard antibiotics, many AMPs are able to rapidly permeate bacteria and cause irreversible damage to their cell membranes, leading to the death of microorganisms [ 10 , 11 ]. In some cases, their action is also intracellular [ 12 , 13 ].…”

Expression and purification of the native C‐amidated antimicrobial peptide maculatin 1.1

“…The molecular mechanism by which Mac1 inhibits bacteria growth is still not fully known although its propensity to interact with bacterial membrane to form helical structures is key. 1,11 NMR and in particular solid-state NMR are powerful techniques to understand the self-assembly mechanism of Mac1 into bacterial membranes. 9,33 Isotopically labelled peptides are usually needed to increase sensitivity and alleviate interference from background signals for in-cell NMR experiment.…”

“…Antimicrobial peptides (AMPs) are seen as promising alternatives to antibiotics in order to restrain the alarming rise in antibiotic resistance. [1][2][3] Because bacteria are less likely to evolve resistance against AMPs due to their targeting of and damage to the cell membrane, AMPs have potential for clinical therapy and pharmaceutical development. [4][5][6][7] Maculatin 1.1 (Mac1, GLFGVLAKVAAHVVPAIAEHF-NH 2 ) is a cationic AMP isolated from the skin glands of the Australian tree frog Litoria genimaculata.…”