Recktenwald Matthias, Kaur Muskanjot, Benmassaoud Mohammed M, Copling Aryanna, Khanna Tulika, Curry Michael, Cortes Dennise, Fleischer Gilbert, Carabetta Valerie J, Vega Sebastián L
Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA.
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
Pharmaceutics. 2024 Jun 27;16(7):860. doi: 10.3390/pharmaceutics16070860.
() is an opportunistic pathogen that lives on surfaces and skin and can cause serious infections inside the body. Antimicrobial peptides (AMPs) are part of the innate immune system and can eliminate pathogens, including bacteria and viruses, and are a promising alternative to antibiotics. Although studies have reported that AMP-functionalized hydrogels can prevent bacterial adhesion and biofilm formation, AMP dosing and the combined effects of multiple AMPs are not well understood. Here, three AMPs with different antibacterial properties were synthesized and the soluble minimum inhibitory concentrations (MICs) of each AMP against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) were determined. Hydrogels with immobilized AMPs at their MIC (DD-RIP 27.5 µM; indolicidin 43.8 µM; P10 120 µM) were effective in preventing MRSA adhesion and biofilm formation. Checkerboard AMP screens identified synergy between indolicidin (3.1 µM) and P10 (12.5 µM) based on soluble fractional inhibitory concentration indices (FICIs) against MRSA, and hydrogels formed with these AMPs at half of their synergistic concentrations (total peptide concentration, 7.8 µM) were highly efficacious in killing MRSA. Mammalian cells cultured atop these hydrogels were highly viable, demonstrating that these AMP hydrogels are biocompatible and selectively eradicate bacteria, based on soluble checkerboard-screening data.
（某病原体）是一种机会致病菌，寄生于体表和皮肤，可在体内引发严重感染。抗菌肽（AMPs）是先天免疫系统的一部分，能够清除包括细菌和病毒在内的病原体，是一种很有前景的抗生素替代品。尽管已有研究报道AMPs功能化水凝胶可防止细菌黏附和生物膜形成，但AMPs的给药剂量以及多种AMPs的联合作用尚不清楚。在此，合成了三种具有不同抗菌特性的AMPs，并测定了每种AMPs对甲氧西林敏感（MSSA）和耐甲氧西林（MRSA）菌株的可溶性最低抑菌浓度（MICs）。固定有处于MIC浓度的AMPs的水凝胶（DD-RIP为27.5 µM；吲哚杀菌素为43.8 µM；P10为120 µM）可有效防止MRSA黏附和生物膜形成。棋盘式AMPs筛选基于针对MRSA的可溶性分数抑菌浓度指数（FICIs）确定了吲哚杀菌素（3.1 µM）和P10（12.5 µM）之间的协同作用，并且由这些处于协同浓度一半的AMPs形成的水凝胶（总肽浓度为7.8 µM）在杀灭MRSA方面非常有效。在这些水凝胶上培养的哺乳动物细胞具有很高的活力，这表明基于可溶性棋盘式筛选数据，这些AMPs水凝胶具有生物相容性且能选择性地根除细菌。
