Lung-Targeting Lysostaphin Microspheres for Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment and Prevention,ACS Nano

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Lung-Targeting Lysostaphin Microspheres for Methicillin-Resistant Staphylococcus aureus Pneumonia Treatment and Prevention
ACS Nano ( IF 15.8 ) Pub Date : 2021-09-28 , DOI: 10.1021/acsnano.1c06460
Xiuhui Lin ₁ , Jian He ₂ , Wanlin Li ₂ , Yuchen Qi ₂ , Huiqun Hu ₁ , Dongxiao Zhang ₂ , Feng Xu ₁ , Xiaoyuan Chen _{3,

4,

5} , Min Zhou _{1,

2,

6,

7}

Affiliation

Multifunctional antimicrobial strategies are urgently needed to treat methicillin-resistant Staphylococcus aureus (MRSA) caused pneumonia due to its increasing resistance, enhanced virulence, and high pathogenicity. Here, we report that lysostaphin, a bacteriolytic enzyme, encapsulated within poly(lactic-co-glycolic acid) microspheres (LyIR@MS) specially treats planktonic MRSA bacteria, mature biofilms, and related pneumonia. Optimized LyIR@MS with suitable diameters could deliver a sufficient amount of lysostaphin to the lung without a decrease in survival rate after intravenous injection. Furthermore, the degradable properties of the carrier make it safe for targeted release of lysostaphin to eliminate MRSA, repressing the expression of virulence genes and improving the sensitivity of biofilms to host neutrophils. In the MRSA pneumonia mouse model, treatment or prophylaxis with LyIR@MS significantly improved survival rate and relieved inflammatory injury without introducing adverse events. These findings suggest the clinical translational potential of LyIR@MS for the treatment of MRSA-infected lung diseases.

中文翻译：

肺靶向溶葡萄球菌素微球用于耐甲氧西林金黄色葡萄球菌肺炎的治疗和预防

由于耐甲氧西林金黄色葡萄球菌（MRSA）耐药性增加、毒力增强和致病性高，因此迫切需要多功能抗菌策略来治疗其引起的肺炎。在这里，我们报告说，溶葡球菌酶，一溶菌酶，内聚（乳酸-封装合作-乙醇酸）微球（LyIR@MS）专门治疗浮游MRSA细菌、成熟生物膜和相关肺炎。具有合适直径的优化 LyIR@MS 可以向肺部输送足量的溶葡萄球菌素，而不会降低静脉注射后的存活率。此外，载体的可降解特性使其能够安全地靶向释放溶葡萄球菌素以消除 MRSA，抑制毒力基因的表达并提高生物膜对宿主中性粒细胞的敏感性。在 MRSA 肺炎小鼠模型中，使用 LyIR@MS 进行治疗或预防可显着提高存活率并减轻炎症损伤，而不会引入不良事件。这些发现表明 LyIR@MS 在治疗 MRSA 感染的肺部疾病方面具有临床转化潜力。

更新日期：2021-10-26

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