Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model
Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model
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DOI：
10.1038/s41598-020-64352-2
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发表时间：
2020-04-29
影响因子：
4.6
通讯作者：
Seleem, Mohamed N.
中科院分区：
文献类型：
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作者：
Mohammad, Haroon;Abutaleb, Nader S.;Seleem, Mohamed N.
压疮 (PU) 经常发生在行动不便的个体中，包括住院或肥胖的患者。当抗生素耐药细菌，特别是耐甲氧西林金黄色葡萄球菌 (MRSA) 感染时，PU 的解决具有挑战性。在这项研究中，我们研究了重新利用金诺芬治疗 MRSA 感染的压疮的潜力。在存在较高细菌接种量 (10(7) CFU/mL) 或降低标准培养基中的 pH 值以模拟皮肤表面存在的环境的情况下，Auranofin 针对金黄色葡萄球菌菌株（包括 MRSA）的体外活性不会受到影响。此外，通过多步耐药性选择实验，金黄色葡萄球菌在重复暴露两周后并未对金诺芬产生耐药性。相比之下，金黄色葡萄球菌对莫匹罗星的耐药性迅速出现。此外，金诺芬在体外对测试的三种金黄色葡萄球菌菌株表现出长期抗生素后效应（PAE）。值得注意的是，仅治疗四天后，局部金诺芬就完全根除肥胖小鼠感染 PU 中的 MRSA（减少 8-log(10)）。这优于临床上用于治疗感染 PU 的局部莫匹罗星（减少 1.96-log(10)）和口服克林霉素（减少 1.24-log(10)）。本研究强调了金诺芬作为治疗感染金黄色葡萄球菌的轻至中度PU的潜力进行进一步研究。
Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin's in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (10(7) CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log(10) reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log(10) reduction) and oral clindamycin (1.24-log(10) reduction), which are used to treat infected PUs clinically. The present study highlights auranofin's potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.