The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.

包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的耐多药（MDR）生物的发生对公共健康构成了严重威胁。抗生素耐药性的发展正在赶超新疗法的发展，而迅速渗透细菌的替代药物在治疗MDR感染方面具有巨大的潜力。一类新的糖聚合物包括聚阳离子聚N（乙酰基，精氨酰基）葡糖胺（PAAG）正在开发中，作为治疗MRSA感染的传统抗生素策略的替代方法。这项研究证明了PAAG对临床分离的甲氧西林和耐Mupirocin的金黄色葡萄球菌的抗菌活性。耐多药小号。金黄色被PAAG迅速杀死，PAAG在≤12小时内以对哺乳动物细胞无毒的剂量完全根除了所有测试菌株的88％（15/17）（CFU降低了6个对数）。PAAG还使所有临床MRSA菌株（17/17）对奥沙西林敏感，如观察到的奥沙西林MIC降低到抗生素耐药性断裂点以下所表明的那样。通过测量细菌细胞对碘化丙啶（PI）的吸收，研究了PAAG和标准抗生素（包括万古霉素，奥沙西林，莫匹罗星和杆菌肽）对MRSA渗透性的影响。抗菌素耐药性研究表明，S。金黄色葡萄球菌对PAAG的耐药性比对莫匹罗星的耐药性慢，但与杆菌肽相似。观察到PAAG使抗药性S重新敏感。从多通道抗性研究的第13和20代中取样的金黄色葡萄球菌菌株将莫匹罗星和杆菌肽的MIC降低到其临床敏感性断点以下。这类细菌可渗透的糖聚合物可为对抗多药耐药细菌提供新的工具。