Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm Heteromastus filiformis: Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential
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Published:2023-12-14
Issue:12
Volume:21
Page:639
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ISSN:1660-3397
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Container-title:Marine Drugs
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language:en
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Short-container-title:Marine Drugs
Author:
Panteleev Pavel V.1ORCID, Safronova Victoria N.1, Duan Shuting12, Komlev Alexey S.3, Bolosov Ilia A.1ORCID, Kruglikov Roman N.1, Kombarova Tatiana I.4, Korobova Olga V.4, Pereskokova Eugenia S.4, Borzilov Alexander I.4ORCID, Dyachenko Igor A.5ORCID, Shamova Olga V.3ORCID, Huang Yu2ORCID, Shi Qiong26ORCID, Ovchinnikova Tatiana V.17ORCID
Affiliation:
1. M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia 2. Shenzhen Key Lab of Marine Genomics, Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic Animals, BGI Academy of Marine Sciences, BGI Marine, Shenzhen 518081, China 3. Institute of Experimental Medicine, WCRC “Center for Personalized Medicine”, 197022 St. Petersburg, Russia 4. State Research Center for Applied Microbiology & Biotechnology (SRCAMB), 142279 Obolensk, Russia 5. The Branch of M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 142290 Pushchino, Russia 6. Laboratory of Aquatic Genomics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518057, China 7. Department of Biotechnology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Abstract
Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids. In this paper, we report the discovery of 13 novel BRICHOS-related peptides, ranging from 18 to 91 amino acid residues in length, in the cosmopolitan marine worm Heteromastus filiformis with the assistance of transcriptome mining. Two characteristic peptides with a low homology in relation to known AMPs—the α-helical amphiphilic linear peptide, consisting of 28 amino acid residues and designated as HfBRI-28, and the 25-mer β-hairpin peptide, specified as HfBRI-25 and having a unique structure stabilized by two disulfide bonds—were obtained and analyzed as potential antimicrobials. Interestingly, both peptides showed the ability to kill bacteria via membrane damage, but mechanisms of their action and spectra of their activity differed significantly. Being non-cytotoxic towards mammalian cells and stable to proteolysis in the blood serum, HfBRI-25 was selected for further in vivo studies in a lethal murine model of the Escherichia coli infection, where the peptide contributed to the 100% survival rate in animals. A high activity against uropathogenic strains of E. coli (UPEC) as well as a strong ability to kill bacteria within biofilms allow us to consider the novel peptide HfBRI-25 as a promising candidate for the clinical therapy of urinary tract infections (UTI) associated with UPEC.
Funder
Ministry of Science and Higher Education of the Russian Federation
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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