Federal Research and Clinical Center of Physical Chemical Medicine of Federal Medical Biological Agency, Moscow 119435, Russia.
Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Moscow 141701, Russia.
Int J Mol Sci. 2020 Sep 27;21(19):7141. doi: 10.3390/ijms21197141.
Antimicrobial peptides (AMPs) are considered a promising new class of anti-infectious agents. This study reports new antimicrobial peptides derived from the microbiome identified by a computational analysis method applied to the metagenome. The identified AMPs possess a strong antimicrobial activity against Gram-positive and Gram-negative bacteria (MIC range: 5.3 to 22.4 μM), including , an opportunistic coagulase-negative pathogen. The secondary structure analysis of peptides via CD spectroscopy showed that all the AMPs except pept_352 have mostly disordered structures that do not change under different conditions. For peptide pept_352, the α-helical content increases in the membrane environment. The examination of the mechanism of action of peptides suggests that peptide pept_352 exhibits a direct membranolytic activity. Furthermore, the cytotoxicity assay demonstrated that the nontoxic peptide pept_1545 is a promising candidate for drug development. Overall, the analysis method implemented in the study may serve as an effective tool for the identification of new AMPs.
抗菌肽(AMPs)被认为是一类有前途的新型抗感染药物。本研究报道了通过应用于宏基因组的计算分析方法从微生物组中鉴定出的新型抗菌肽。鉴定出的 AMP 对革兰氏阳性和革兰氏阴性菌具有很强的抗菌活性(MIC 范围:5.3 至 22.4 μM),包括一种机会性病原体凝固酶阴性葡萄球菌。通过圆二色性(CD)光谱对肽的二级结构分析表明,除了肽 pept_352 外,所有 AMP 都具有主要无序结构,在不同条件下不会发生变化。对于肽 pept_352,在膜环境中α-螺旋含量增加。对肽作用机制的研究表明,肽 pept_352 表现出直接的膜溶解活性。此外,细胞毒性试验表明,非毒性肽 pept_1545 是药物开发的有前途的候选物。总的来说,研究中实施的分析方法可以作为鉴定新型 AMP 的有效工具。