The Hirudo Medicinalis Microbiome Is a Source of New Antimicrobial Peptides

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7141
• Main Authors: Grafskaia, Ekaterina, Pavlova, Elizaveta, Babenko, Vladislav V, Latsis, Ivan, Malakhova, Maja, Lavrenova, Victoria, Bashkirov, Pavel, Belousov, Dmitrii, Klinov, Dmitry, Lazarev, Vassili
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - metabolism; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Bacteria; bioinformatic analysis; Cell Line; Cell Survival - drug effects; Circular Dichroism; Coagulase; Computer applications; Cytotoxicity; Drug development; Drug Discovery - methods; E coli; Fibroblasts - drug effects; Genomes; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Hirudo medicinalis; Hirudo medicinalis - metabolism; Hirudo medicinalis - microbiology; Identification and classification; Metagenome; Mice; Microbial Sensitivity Tests; microbiome; Microbiomes; Microbiota - physiology; Microorganisms; Minimum inhibitory concentration; Opportunist infection; Pathogens; Peptides; Protein Conformation, alpha-Helical; Protein structure; Proteins; Secondary structure; Spectroscopy; Spectrum analysis; Structural analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.