Bacterial Toxin-Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin-Resistant Staphylococcus aureus (MRSA) Infection.

Bacterial Toxin-Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin-Resistant Staphylococcus aureus (MRSA) Infection.
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细菌毒素触发的抗生素从囊泡体中释放可保护果蝇模型免受致命的耐甲氧西林金黄色葡萄球菌(MRSA)感染。

DOI:
10.1002/adhm.202200036
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发表时间:
2022-07
影响因子:
10
通讯作者:
Stevens MM
Stevens MM
中科院分区:
工程技术1区
文献类型:
--
作者:
Tonkin RL;Klöckner A;Najer A;Simoes da Silva CJ;Echalier C;Dionne MS;Edwards AM;Stevens MM

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抗生素耐药性是一个严重的全球健康威胁,因此需要迅速采取行动,开发新的治疗方法,包括微型药物输送系统。本文中,开发了分级微粒系统以实现细菌活化的单抗生素和双抗生素药物递送,用于预防耐甲氧西林金黄色葡萄球菌(MRSA)细菌感染。所设计的系统是基于一个capsosome结构,它由一个介孔二氧化硅微粒涂层在交替层的带相反电荷的聚合物和脂质体负载。所述囊体被工程化并且显示出在由Agr群体感应系统控制的MRSA毒素的存在下释放其药物有效载荷。MRSA激活的万古霉素单一药物递送和万古霉素与抗菌肽一起的协同双重递送在体外成功地杀死MRSA。使用黑腹果蝇MRSA感染模型在体内证实了在细菌存在下衣壳选择性递送其货物的能力,产生杀菌作用以保护宿主生物体。因此,胶囊体作为一种通用的多药,亚区室化的微粒系统,用于预防耐药细菌感染,具有潜在的应用,以保护伤口或医疗器械植入物免受感染。
Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria-activated single- and dual-antibiotic drug delivery for preventing methicillin-resistant Staphylococcus aureus (MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic-loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA-activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic-resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.
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