Linzner Nico, Antelmann Haike
Freie Universität Berlin, Institute for Biology-Microbiology, Berlin, Germany.
Front Microbiol. 2021 Aug 12;12:731564. doi: 10.3389/fmicb.2021.731564. eCollection 2021.
Methicillin-resistant (MRSA) isolates are often resistant to multiple antibiotics and pose a major health burden due to limited treatment options. The novel AGXX® surface coating exerts strong antimicrobial activity and successfully kills multi-resistant pathogens, including MRSA. The mode of action of AGXX® particles involves the generation of reactive oxygen species (ROS), which induce an oxidative and metal stress response, increased protein thiol-oxidations, protein aggregations, and an oxidized bacillithiol (BSH) redox state in . In this work, we report that the AGXX® particle size determines the effective dose and time-course of USA300JE2 killing. We found that the two charges AGXX®373 and AGXX®383 differ strongly in their effective concentrations and times required for microbial killing. While 20-40 μg/ml AGXX®373 of the smaller particle size of 1.5-2.5 μm resulted in >99.9% killing after 2 h, much higher amounts of 60-80 μg/ml AGXX®383 of the larger particle size of >3.2 μm led to a >99% killing of USA300JE2 within 3 h. Smaller AGXX® particles have a higher surface/volume ratio and therefore higher antimicrobial activity to kill at lower concentrations in a shorter time period compared to the larger particles. Thus, in future preparations of AGXX® particles, the size of the particles should be kept at a minimum for maximal antimicrobial activity.
耐甲氧西林金黄色葡萄球菌(MRSA)分离株通常对多种抗生素耐药,由于治疗选择有限,构成了重大的健康负担。新型AGXX®表面涂层具有强大的抗菌活性,能成功杀灭包括MRSA在内的多重耐药病原体。AGXX®颗粒的作用方式涉及活性氧(ROS)的产生,ROS会在……中引发氧化和金属应激反应、增加蛋白质硫醇氧化、蛋白质聚集以及氧化型杆菌硫醇(BSH)的氧化还原状态。在这项研究中,我们报告了AGXX®颗粒大小决定了对USA300JE2的有效杀灭剂量和时间进程。我们发现两种电荷的AGXX®373和AGXX®383在有效浓度和杀灭微生物所需时间上有很大差异。粒径为1.5 - 2.5μm的较小的AGXX®373,20 - 40μg/ml在2小时后导致>99.9%的杀灭率,而粒径大于3.2μm的较大的AGXX®383,60 - 80μg/ml在3小时内导致对USA300JE2>99%的杀灭率。与较大颗粒相比,较小的AGXX®颗粒具有更高的表面积/体积比,因此在较低浓度下能在更短时间内具有更高的抗菌活性来杀灭细菌。因此,在未来AGXX®颗粒的制备中,颗粒大小应保持在最小以获得最大抗菌活性。