Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States; Center for Environmental Nanoscience and Risk (CENR), University of South Carolina, Columbia, SC, United States; Department of Biological Development of Shatt Al-Arab & N. Arabian Gulf, Marine Science Centre, University of Basrah, Basrah, Iraq.
Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States.
J Glob Antimicrob Resist. 2020 Sep;22:811-817. doi: 10.1016/j.jgar.2020.06.023. Epub 2020 Jul 9.
The aim of this study was to examine how the concentrated delivery of less effective antibiotics, such as the β-lactam penicillin G, by linkage to nanoparticles (NPs), could influence the killing efficiency against various pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and other multidrug resistant (MDR) strains.
The β-lactam antibiotic penicillin G (PenG) was passively sorbed to fluorescent polystyrene NPs (20nm) that were surface-functionalized with carboxylic acid (COO-NPs) or sulfate groups (SO-NPs) to form a PenG-NP complex. Antimicrobial activities of PenG-NPs were evaluated against Gram-negative and Gram-positive bacteria, including antibiotic resistant strains. Disc diffusion, microdilution assays and live/dead staining were performed for antibacterial assessments.
The results showed that bactericidal activities of PenG-NP complexes were statistically significantly (P<0.05) enhanced against Gram-negative and Gram-positive strains, including MRSA and MDR strains. Fluorescence imaging verified that NPs comigrated with antibiotics throughout clear zones of MIC agar plate assays. The increased bactericidal abilities of NP-linked antibiotics are hypothesized to result from the greatly increased densities of antibiotic delivered by each NP to a given bacterial cell (compared with solution concentrations of antibiotic), which overwhelms the bacterial resistance mechanism(s).
As a whole, PenG-NP complexation demonstrated a remarkable activity against different pathogenic bacteria, including MRSA and MDR strains. We term this the 'grenade hypothesis'. Further testing and development of this approach will provide validation of its potential usefulness for controlling antibiotic-resistant bacterial infections.
本研究旨在探讨将效果较差的抗生素（如β-内酰胺类青霉素 G）通过与纳米颗粒（NPs）连接进行集中输送，如何影响其对各种致病菌（包括耐甲氧西林金黄色葡萄球菌（MRSA）和其他多药耐药（MDR）菌株）的杀伤效率。
将β-内酰胺类抗生素青霉素 G（PenG）被动吸附到荧光聚苯乙烯 NPs（20nm）上，这些 NPs 表面用羧酸（COO-NPs）或硫酸盐（SO-NPs）官能化，形成 PenG-NP 复合物。通过抑菌圈扩散、微量稀释测定和死活染色法评估 PenG-NP 对革兰氏阴性和革兰氏阳性细菌（包括抗生素耐药株）的抗菌活性。
结果表明，PenG-NP 复合物对革兰氏阴性和革兰氏阳性菌株（包括 MRSA 和 MDR 菌株）的杀菌活性具有统计学显著（P<0.05）增强。荧光成像证实 NPs 与抗生素在 MIC 琼脂平板测定的透明区中共同迁移。NP 连接抗生素的杀菌能力增强，据推测是由于每个 NP 递送到给定细菌细胞的抗生素密度大大增加（与抗生素溶液浓度相比），从而克服了细菌耐药机制。
总体而言，PenG-NP 络合对不同的致病菌（包括 MRSA 和 MDR 菌株）表现出显著的活性。我们将这种现象称为“手榴弹假说”。进一步的测试和这种方法的开发将为控制抗生素耐药性细菌感染的潜在用途提供验证。
