Huang Tao, Linklater Denver, Li Xin, Gamage Shaveen S B, Alkazemi Hazem, Farrugia Brooke, Heath Daniel E, O'Brien-Simpson Neil M, O'Connor Andrea J
Department of Biomedical Engineering, Graeme Clark Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia.
ACTV Research Group, Melbourne Dental School and The Bio21 Institute of Molecular Science and Biotechnology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
ACS Appl Mater Interfaces. 2024 Dec 18;16(50):68996-69010. doi: 10.1021/acsami.4c17157. Epub 2024 Dec 5.
The growing threat of antimicrobial resistance (AMR) necessitates innovative strategies beyond conventional antibiotics. In response, we developed a rapid one-step method to sythesize antimicrobial peptide (AMP) ε-poly--lysine stabilized selenium nanoparticles (ε-PL-Se NPs). These polycrystalline NPs with highly positive net surface charges, exhibited superior antimicrobial activity against a broad panel of pathogens, including the Gram-positive and -negative bacteria , , , and and their drug-resistant counterparts, as well as the yeast . Notably, 10PL-Se NPs exhibited 6-log reduction of methicillin-resistant (MRSA) at a concentration of 5 μg/mL within 90 min, with minimum bactericidal concentrations (MBCs) below 50 μg/mL for all tested bacterial strains. The minimum fungicidal concentration (MFC) of 10PL-Se NPs against was 26 ± 10 μg/mL. Crucially, bacteria exposed to ε-PL-Se NPs exhibited significantly delayed resistance development compared to the conventional antibiotic kanamycin. developed resistance to kanamycin after ∼72 generations, whereas resistance to 10PL-Se NPs emerged after ∼216 generations. Remarkably, showed resistance to kanamycin after ∼39 generations but failed to develop resistance to 10PL-Se NPs even after 300 generations. This work highlights the synergistic interactions between ε-PL and Se NPs, offering a robust and scalable strategy to combat AMR.
抗菌耐药性（AMR）日益增长的威胁使得除传统抗生素之外的创新策略成为必要。作为回应，我们开发了一种快速一步法来合成抗菌肽（AMP）ε-聚赖氨酸稳定的硒纳米颗粒（ε-PL-Se NPs）。这些具有高度正净表面电荷的多晶纳米颗粒对包括革兰氏阳性和阴性细菌、 、 、 和 及其耐药对应物以及酵母在内的多种病原体表现出卓越的抗菌活性。值得注意的是，ε-PL-Se NPs在90分钟内以5μg/mL的浓度使耐甲氧西林金黄色葡萄球菌（MRSA）减少了6个对数，所有测试细菌菌株的最低杀菌浓度（MBC）均低于50μg/mL。ε-PL-Se NPs对 的最低杀真菌浓度（MFC）为26±10μg/mL。至关重要的是，与传统抗生素卡那霉素相比，暴露于ε-PL-Se NPs的细菌表现出显著延迟的耐药性发展。 在约72代后对卡那霉素产生耐药性，而对ε-PL-Se NPs的耐药性在约216代后出现。值得注意的是， 在约39代后对卡那霉素产生耐药性，但即使在300代后也未对ε-PL-Se NPs产生耐药性。这项工作突出了ε-聚赖氨酸和硒纳米颗粒之间的协同相互作用，为对抗抗菌耐药性提供了一种强大且可扩展的策略。
