Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg SE-412 96, Sweden; Centre for Antibiotic Resistance Research in Gothenburg (CARe), SE-405 30 Gothenburg, Sweden.
Amferia AB, AZ BioVentureHub, Mölndal SE-431 83, Sweden.
Int J Pharm. 2024 Oct 25;664:124630. doi: 10.1016/j.ijpharm.2024.124630. Epub 2024 Aug 30.
The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA's minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.
抗生素耐药菌的出现，如耐甲氧西林金黄色葡萄球菌（MRSA），需要新的方法来对抗感染。植入物和伤口敷料等医疗器械经常与抗生素一起使用，这促使人们开发出具有结合抗菌作用的抗菌生物材料，与传统抗生素相结合。本研究探讨了将抗菌肽（AMP）功能化水凝胶颗粒与传统抗生素万古霉素（VCM）和苯唑西林（OXA）联合使用对金黄色葡萄球菌和 MRSA 的协同抗菌作用。所使用的 AMP，RRPRPRPRPWWWW-NH，先前已证明具有广谱活性和与水凝胶底物结合时的增强稳定性。在这里，棋盘试验显示游离 AMP 与 VCM 和 OXA 之间对金黄色葡萄球菌和 MRSA 均具有相加和协同作用。值得注意的是，AMP-OXA 联合对 MRSA 显示出显著的协同作用，当与游离 AMP 联合使用时，OXA 的最小抑菌浓度（MIC）降低了 512 倍。当 AMP 被共价固定在水凝胶颗粒上时，观察到对 MRSA 的协同作用仍然存在；然而，OXA MIC 降低了 64 倍。尽管如此，OXA-AMP 水凝胶颗粒组合对 MRSA 仍具有相当大的协同潜力，这是一种对 OXA 耐药的菌株，突出了 AMP 功能化材料在增强抗生素疗效方面的潜力。这些发现强调了开发用于未来医疗器械的抗菌生物材料以对抗与生物材料相关的感染和逆转抗菌耐药性的重要性。
