Abstract
Antibiotic resistance is increasing and new strategies are needed to fight infection. Advanced materials are promising tools that can be combined with innovative alternatives to conventional antibiotics to allow more targeted and efficient treatment. In this work, we explored the activity against Staphylococcus epidermidis (S. epidermidis) of the α-helical antimicrobial peptide (AMP) MSI-78(4-20) (KFLKKAKKFGKAFVKIL) when covalently bound to a chitosan coating. The AMP MSI-78(4-20) (17 mer) is an improved version of its parent MSI-78 (22 mer; commercially known as Pexiganan), a cost-effective short AMP, which was demonstrated to be as effective as MSI-78 and less toxic to eukaryotic cells. An MSI-78(4-20)–chitosan coating could be applied in several infection scenarios, ranging from bone implants to wound dressings, as chitosan possesses osteoconductive and hemostatic properties. Cysteine-modified MSI-78(4-20) was covalently immobilized onto the chitosan coating through a succinimidyl-[(N-maleimidopropionamido)-octaethyleneglycol] ester (SM(PEG)8), a heterobifuncional crosslinker, with N-hydroxysuccinimide (NHS) ester and maleimide groups, by its N- and C- termini. The MSI-78(4-20)–chitosan coating demonstrated bactericidal properties independently of the tethering site and an improved performance in the presence of plasma proteins, which mimics conditions that will be encountered in vivo. This AMP–chitosan coating has therefore great potential for applications in medical devices such as implants or even wound dressings.
Highlights
Microbial infections caused by antibiotic-resistant strains are responsible for large numbers of deaths worldwide, and it has been estimated that ten million people will die annually by 2050 in the USA alone if alternatives are not found [1]
We explored the activity of the α-helical antimicrobial peptide (AMP) MSI-78(4-20) (KFLKKAKKFGKAFVKIL)
Immobilization onto chitosan was achieved through the heterobifunctional crosslinker succinimidyl-[(N-maleimidopropionamido)-octaethyleneglycol] ester (SM(PEG)8 ), which is based on a poly(ethylene glycol)8 (PEG)8 core functionalized with N-hydroxysuccinimide (NHS) at one end, and with a maleimide at the other (Figure 1)
Summary
Microbial infections caused by antibiotic-resistant strains are responsible for large numbers of deaths worldwide, and it has been estimated that ten million people will die annually by 2050 in the USA alone if alternatives are not found [1]. Apart from specific resistance mechanisms, bacteria can grow in highly organized communities that form biofilms, which are extremely resistant to conventional antibiotics. This mode of growth may occur on a surface such as an implant or a catheter, or at any place in the body where host defenses are compromised (e.g., chronic wounds with impaired blood supply) [2]. Advanced materials such as coatings, hydrogels, and nanoparticles have been combined. Most AMPs, namely cationic AMPs, act via nonspecific interactions with negatively charged bacterial membranes, causing membrane disruption or trans-membrane pore formation, leading to cell lysis and death [4]
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