Abstract
There is a considerable interest in understanding the function of antimicrobial peptides (AMPs), but the details of their mode of action is not fully understood. This motivates extensive efforts in determining structural and mechanistic parameters for AMP’s interaction with lipid membranes. In this study we show that oriented-sample 31P solid-state NMR spectroscopy can be used to probe the membrane perturbations and -disruption by AMPs. For two AMPs, alamethicin and novicidin, we observe that the majority of the lipids remain in a planar bilayer conformation but that a number of lipids are involved in the peptide anchoring. These lipids display reduced dynamics. Our study supports previous studies showing that alamethicin adopts a transmembrane arrangement without significant disturbance of the surrounding lipids, while novicidin forms toroidal pores at high concentrations leading to more extensive membrane disturbance.
Highlights
The increasing appearance of multidrug resistant bacterial strains during past decades has caused tremendous problems with treating bacterial infections
Ratios Before turning to the 31P investigations of the two peptide-lipid complexes, we investigated the pore formation of alamethicin and novicidin at high P:L ratios
We prepared samples of 15N-Aib8 alamethicin and 15N-Ile14 novicidin at high peptide-to-lipid (P:L) ratios (,1:15) and recorded the oriented-sample 15N solid-state NMR spectra shown in Fig. 3a and 3b
Summary
The increasing appearance of multidrug resistant bacterial strains during past decades has caused tremendous problems with treating bacterial infections. In the past 50 years, the resistance to every new antibiotic appeared within a few years of its introduction [1] and has been responsible for increased mortality and morbidity of patients as well as for increased treatment costs [2] This fact has prompted scientists to search for alternative and potentially more effective antimicrobial agents with novel mechanisms of action. A promising alternative includes so-called antimicrobial peptides (AMP’s) [3]. These short peptides (,10– 60 amino acid residues) [4] are abundant in Nature, constituting part of the innate immune response towards invading pathogens in a broad spectrum of organisms [5]. Among the most extensively studied AMP’s range peptides such as alamethicin [6], pardaxin [7], PGLA [8], gramicidin [9], and novicidin [10] to name a few
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