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α-半乳糖结合适体与万古霉素协同降低体内感染

Alpha-Gal Bound Aptamer and Vancomycin Synergistically Reduce Infection In Vivo.

作者信息

Doherty Matthew K, Shaw Claire, Woods Leslie, Weimer Bart C

机构信息

Population Health and Reproduction, University of California Davis, Davis, CA 95616, USA.

California Animal Health and Food Safety Laboratory, University of California Davis, Davis, CA 95616, USA.

出版信息

Microorganisms. 2023 Jul 8;11(7):1776. doi: 10.3390/microorganisms11071776.

Abstract

Methicillin-resistant (MRSA) is a pervasive and persistent threat that requires the development of novel therapies or adjuvants for existing ones. Aptamers, small single-stranded oligonucleotides that form 3D structures and can bind to target molecules, provide one possible therapeutic route, especially when presented in combination with current antibiotic applications. BALB/c α-1, 3-galactosyltransferase (-/-) knockout (GTKO) mice were infected with MRSA via tail vein IV and subsequently treated with the αSA31 aptamer (n = 4), vancomycin (n = 12), or αSA31 plus vancomycin (n = 12), with split doses in the morning and evening. The heart, lungs, liver, spleen, and kidneys were harvested upon necropsy for histological and qPCR analysis. All mice treated with αSA31 alone died, whereas 5/12 mice treated with vancomycin alone and 7/12 mice treated with vancomycin plus αSA31 survived the course of the experiment. The treatment of MRSA-infected mice with Vancomycin and an adjuvant aptamer αSA31 reduced disease persistence and dispersion as compared to treatment with either vancomycin SA31 alone, indicating the combination of antibiotic and specifically targeted αSA31 aptamer could be a novel way to control MRSA infection. The data further indicate that aptamers may serve as a potential therapeutic option for other emerging antibiotic resistant pathogens.

摘要

耐甲氧西林金黄色葡萄球菌(MRSA)是一种普遍且持续存在的威胁,需要开发新的治疗方法或现有疗法的辅助剂。适体是形成三维结构并能与靶分子结合的小单链寡核苷酸,提供了一种可能的治疗途径,特别是与当前抗生素联合应用时。通过尾静脉注射将BALB/c α-1,3-半乳糖基转移酶(-/-)基因敲除(GTKO)小鼠感染MRSA,随后用αSA31适体(n = 4)、万古霉素(n = 12)或αSA31加万古霉素(n = 12)进行治疗,早晚分剂量给药。尸检时采集心脏、肺、肝、脾和肾脏进行组织学和qPCR分析。单独用αSA31治疗的所有小鼠均死亡,而单独用万古霉素治疗的12只小鼠中有5只存活,用万古霉素加αSA31治疗的12只小鼠中有7只在实验过程中存活。与单独使用万古霉素或αSA31治疗相比,用万古霉素和辅助适体αSA31治疗MRSA感染的小鼠可降低疾病的持续性和扩散,表明抗生素与特异性靶向αSA31适体的联合可能是控制MRSA感染的一种新方法。数据进一步表明,适体可能是其他新出现的抗生素耐药病原体的潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e528/10383818/618851c464db/microorganisms-11-01776-g001.jpg

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