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具有强效抗肺炎球菌活性并与青霉素协同作用的设计肽的体内疗效及分子对接

In vivo efficacy and molecular docking of designed peptide that exhibits potent antipneumococcal activity and synergises in combination with penicillin.

作者信息

Le Cheng-Foh, Yusof Mohd Yasim Mohd, Hassan Mahmood Ameen Abdulla, Lee Vannajan Sanghiran, Isa Diyana Mohd, Sekaran Shamala Devi

机构信息

Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Sci Rep. 2015 Jul 9;5:11886. doi: 10.1038/srep11886.

Abstract

We have previously designed a series of antimicrobial peptides (AMPs) and in the current study, the in vivo therapeutic efficacy and toxicity were investigated. Among all the peptides, DM3 conferred protection to a substantial proportion of the lethally infected mice caused by a strain of penicillin-resistant Streptococcus pneumoniae. Synergism was reported and therapeutic efficacy was significantly enhanced when DM3 was formulated in combination with penicillin (PEN). No toxicity was observed in mice receiving these treatments. The in silico molecular docking study results showed that, DM3 has a strong affinity towards three protein targets; autolysin and pneumococcal surface protein A (pspA). Thus AMPs could serve as supporting therapeutics in combination with conventional antibiotics to enhance treatment outcome.

摘要

我们之前设计了一系列抗菌肽(AMPs),在本研究中,对其体内治疗效果和毒性进行了研究。在所有肽中,DM3对相当比例由一株耐青霉素肺炎链球菌引起的致死性感染小鼠起到了保护作用。有报道称,当DM3与青霉素(PEN)联合使用时具有协同作用,治疗效果显著增强。接受这些治疗的小鼠未观察到毒性。计算机模拟分子对接研究结果表明,DM3对三个蛋白质靶点具有很强的亲和力;自溶素和肺炎球菌表面蛋白A(pspA)。因此,抗菌肽可作为辅助治疗药物与传统抗生素联合使用,以提高治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5b9/4496672/ebe8c1cc2bf0/srep11886-f1.jpg

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