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Potent Activity of Hybrid Arthropod Antimicrobial Peptides Linked by Glycine Spacers
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SYSNO ASEP 0555185 Document Type O - Others R&D Document Type Others Title Potent Activity of Hybrid Arthropod Antimicrobial Peptides Linked by Glycine Spacers Author(s) Tonk, M. (DE)
Valdés, James J. (BC-A) RID, ORCID
Cabezas-Cruz, A. (FR)
Vilcinskas, A. (DE)Number of authors 4 Year of issue 2021 Article number 8919 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 16 (2021)Number of pages 17 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords cationic peptides ; model membranes ; protein ; design ; hydrophobicity ; mechanism ; outer ; dynamics ; server ; scale ; insect ; scorpion ; antimicrobial peptide ; hybrid peptide ; glycine spacer ; Escherichia coli Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 000689250700001 EID SCOPUS 85112707113 DOI 10.3390/ijms22168919 Annotation Arthropod antimicrobial peptides (AMPs) offer a promising source of new leads to address the declining number of novel antibiotics and the increasing prevalence of multidrug-resistant bacterial pathogens. AMPs with potent activity against Gram-negative bacteria and distinct modes of action have been identified in insects and scorpions, allowing the discovery of AMP combinations with additive and/or synergistic effects. Here, we tested the synergistic activity of two AMPs, from the dung beetle Copris tripartitus (CopA3) and the scorpion Heterometrus petersii (Hp1090), against two strains of Escherichia coli. We also tested the antibacterial activity of two hybrid peptides generated by joining CopA3 and Hp1090 with linkers comprising two (InSco2) or six (InSco6) glycine residues. We found that CopA3 and Hp1090 acted synergistically against both bacterial strains, and the hybrid peptide InSco2 showed more potent bactericidal activity than the parental AMPs or InSco6. Molecular dynamics simulations revealed that the short linker stabilizes an N-terminal 3(10)-helix in the hybrid peptide InSco2. This secondary structure forms from a coil region that interacts with phosphatidylethanolamine in the membrane bilayer model. The highest concentration of the hybrid peptides used in this study was associated with stronger hemolytic activity than equivalent concentrations of the parental AMPs. As observed for CopA3, the increasing concentration of InSco2 was also cytotoxic to BHK-21 cells. We conclude that AMP hybrids linked by glycine spacers display potent antibacterial activity and that the cytotoxic activity can be modulated by adjusting the nature of the linker peptide, thus offering a strategy to produce hybrid peptides as safe replacements or adjuncts for conventional antibiotic therapy. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2022 Electronic address https://www.mdpi.com/1422-0067/22/16/8919
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