Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, F-31077, Toulouse, France.
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Sci Rep. 2019 Mar 19;9(1):4867. doi: 10.1038/s41598-019-41222-0.
Antibiotic resistance is becoming a global scourge with 700,000 deaths each year and could cause up to 10 million deaths by 2050. As an example, Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. S. epidermidis can form biofilms, which contribute to its pathogenicity when present in intravascular devices. These staphylococci, embedded in the biofilm matrix, are resistant to methicillin, which had long been the recommended therapy and which has nowadays been replaced by less toxic and more stable therapeutic agents. Moreover, current reports indicate that 75 to 90% of Staphylococcus epidermidis isolates from nosocomial infections are methicillin-resistant strains. The challenge of successfully combating antibiotics resistance in biofilms requires the use of compounds with a controlled mode of action that can act in combination with antibiotics. Ruthenium nitrosyl complexes are potential systems for NO release triggered by light. The influence of trans(NO, OH)-RuFT(Cl)(OH)NO on Staphylococcus epidermidis resistant to methicillin is described. The results show a 50% decrease in cell viability in bacteria treated with low concentrations of NO. When combined with methicillin, this low dose of NO dramatically decreases bacterial resistance and makes bacteria 100-fold more sensitive to methicillin.
抗生素耐药性正在成为一个全球性的祸害，每年导致 70 万人死亡，到 2050 年可能导致多达 1000 万人死亡。例如，表皮葡萄球菌已成为与植入医疗器械相关的感染的病原体。表皮葡萄球菌可以形成生物膜，当存在于血管内装置中时，会增加其致病性。这些葡萄球菌嵌入生物膜基质中，对甲氧西林具有耐药性，甲氧西林长期以来一直是推荐的治疗方法，现在已被毒性更小、更稳定的治疗药物所取代。此外，目前的报告表明，75%至 90%的医院感染表皮葡萄球菌分离株为耐甲氧西林菌株。成功对抗生物膜中的抗生素耐药性的挑战需要使用具有受控作用模式的化合物，这些化合物可以与抗生素联合使用。钌亚硝酰配合物是一种潜在的光触发 NO 释放的系统。本文描述了反式（NO，OH）-[RuFT（Cl）（OH）NO]（PF）对耐甲氧西林表皮葡萄球菌的影响。结果表明，用低浓度 NO 处理的细菌的细胞活力降低了 50%。当与甲氧西林联合使用时，这种低剂量的 NO 可显著降低细菌的耐药性，使细菌对甲氧西林的敏感性提高 100 倍。
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