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Opossum Cathelicidins Exhibit Antimicrobial Activity Against a Broad Spectrum of Pathogens Including West Nile Virus.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Mar 03; Vol. 11, pp. 347. Date of Electronic Publication: 2020 Mar 03 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- This study aimed to characterize cathelicidins from the gray short-tailed opossum in silico and experimentally validate their antimicrobial effects against various pathogenic bacteria and West Nile virus (WNV). Genome-wide in silico analysis against the current genome assembly of the gray short-tailed opossum yielded 56 classical antimicrobial peptides (AMPs) from eight different families, among which 19 cathelicidins, namely ModoCath1 - 19, were analyzed in silico to predict their antimicrobial domains and three of which, ModoCath1, -5, and -6, were further experimentally evaluated for their antimicrobial activity, and were found to exhibit a wide spectrum of antimicroial effects against a panel of gram-positive and gram-negative bacterial strains. In addition, these peptides displayed low-to-moderate cytotoxicity in mammalian cells as well as stability in serum and various salt and pH conditions. Circular dichroism analysis of the spectra resulting from interactions between ModoCaths and lipopolysaccharides (LPS) showed formation of a helical structure, while a dual-dye membrane disruption assay and scanning electron microscopy analysis revealed that ModoCaths exerted bactericidal effects by causing membrane damage. Furthermore, ModoCath5 displayed potent antiviral activity against WNV by inhibiting viral replication, suggesting that opossum cathelicidins may serve as potentially novel antimicrobial endogenous substances of mammalian origin, considering their large number. Moreover, analysis of publicly available RNA-seq data revealed the expression of eight ModoCaths from five different tissues, suggesting that gray short-tailed opossums may be an interesting source of cathelicidins with diverse characteristics.<br /> (Copyright © 2020 Cho, Yum, Larivière, Lévêque, Le, Ahn, Jeon, Hong, Soundrarajan, Kim, Bodet and Park.)
- Subjects :
- Amino Acid Sequence
Animals
Cathelicidins chemistry
Cathelicidins genetics
Cathelicidins isolation & purification
Cell Membrane drug effects
Cells, Cultured
Circular Dichroism
Computer Simulation
Gram-Negative Bacteria
Gram-Positive Bacteria
HEK293 Cells
Humans
Keratinocytes
Lipopolysaccharides chemistry
MCF-7 Cells
Opossums genetics
Pore Forming Cytotoxic Proteins chemical synthesis
Pore Forming Cytotoxic Proteins genetics
Pore Forming Cytotoxic Proteins isolation & purification
RNA-Seq
Sequence Alignment
Sequence Homology, Amino Acid
Transcriptome
Virus Replication drug effects
Cathelicidins pharmacology
Opossums immunology
West Nile virus genetics
West Nile virus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32194564
- Full Text :
- https://doi.org/10.3389/fimmu.2020.00347