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利用工程化的阳离子两亲性肽 WLBU2 消除抗生素耐药性手术植入物生物膜

Elimination of Antibiotic Resistant Surgical Implant Biofilms Using an Engineered Cationic Amphipathic Peptide WLBU2.

机构信息

Arthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Sci Rep. 2017 Dec 22;7(1):18098. doi: 10.1038/s41598-017-17780-6.

Abstract

Antibiotics are unable to remove biofilms from surgical implants. This high antibiotic tolerance is related to bacterial persisters, a sub-population of bacteria phenotypically tolerant to antibiotics secondary to a reduced metabolic state. WLBU2 is an engineered cationic amphipathic peptide designed to maximize antimicrobial activity with minimal mammalian cell toxicity. The objective of this study was to test the ability of WLBU2 to remove Staphylococcus aureus surgical implant biofilms. WLBU2 effectively treated S. aureus biofilms formed by a variety of clinical MSSA and MRSA strains and created culture-negative implants in the in vitro biofilm model. Blocking bacterial metabolism by inhibiting oxidative phosphorylation did not affect WLBU2 killing compared to decreased killing by cefazolin. In the surgical implant infection animal model, WLBU2 decreased biofilm mass as compared to control, untreated samples. WLBU2 could rapidly eliminate implants in vitro and had sufficient efficacy in vivo with minimal systemic toxicity.

摘要

抗生素无法从手术植入物中去除生物膜。这种高抗生素耐药性与细菌持久体有关,细菌持久体是一种细菌亚群,由于代谢状态降低,对抗生素表现出表型耐受性。WLBU2 是一种经过工程设计的阳离子两亲肽,旨在最大限度地提高抗菌活性,同时将对哺乳动物细胞的毒性降至最低。本研究的目的是测试 WLBU2 去除金黄色葡萄球菌手术植入物生物膜的能力。WLBU2 有效地治疗了由多种临床 MSSA 和 MRSA 菌株形成的金黄色葡萄球菌生物膜,并在体外生物膜模型中创建了无培养物的植入物。与头孢唑林降低杀伤率相比,通过抑制氧化磷酸化来阻断细菌代谢并没有影响 WLBU2 的杀伤率。在手术植入物感染动物模型中,与对照、未处理的样本相比,WLBU2 减少了生物膜量。WLBU2 可以在体外迅速消除植入物,并且在体内具有足够的疗效,同时具有最小的全身毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90d8/5741726/6dfcf30f546c/41598_2017_17780_Fig1_HTML.jpg

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