Antibacterial, antifungal, anticancer activities and structural bioinformatics analysis of six naturally occurring temporins
| Autor: | Xiuqing Wang, Biswajit Mishra, Tamara Lushnikova, Chunfeng Wang, Yingxia Zhang, Jayaram Lakshmaiah Narayana, Timothy R. McGuire, Guangshun Wang, Radha M. Golla |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Antifungal Agents Cell Survival Protein Conformation Physiology 030106 microbiology Antimicrobial peptides Antineoplastic Agents Peptide Moths Gram-Positive Bacteria medicine.disease_cause Biochemistry Article 03 medical and health sciences Cellular and Molecular Neuroscience Endocrinology In vivo medicine Animals Humans chemistry.chemical_classification biology Chemistry Proteins medicine.disease biology.organism_classification Hemolysis Temporin Anti-Bacterial Agents Galleria mellonella 030104 developmental biology Staphylococcus aureus Biofilms Peptides Hydrophobic and Hydrophilic Interactions Bacteria Antimicrobial Cationic Peptides HeLa Cells |
| Zdroj: | Peptides. 106:9-20 |
| ISSN: | 0196-9781 |
| Popis: | Antimicrobial peptides are a special class of natural products with potential applications as novel therapeutics. This study focuses on six temporins (four with no activity data and two as positive controls). Using synthetic peptides, we report antibacterial, antifungal, and anticancer activities of temporins-CPa, CPb, 1Ga, 1Oc, 1Ola, and 1SPa. While temporin-1Ga and temporin-1OLa showed higher antifungal and anticancer activity, most of these peptides were active primarily against Gram-positive bacteria. Temporin-1OLa, with the highest cell selectivity index, could preferentially kill methicillin-resistant Staphylococcus aureus (MRSA), consistent with a reduced hemolysis in the presence of bacteria. Mechanistically, temporin-1OLa rapidly killed MRSA by damaging bacterial membranes. Using micelles as a membrane-mimetic model, we determined the three-dimensional structure of temporin-1OLa by NMR spectroscopy. The peptide adopted a two-domain structure where a hydrophobic patch is followed by a classic amphipathic helix covering residues P3-I12. Such a structure is responsible for anti-biofilm ability in vitro and in vivo protection of wax moths Galleria mellonella from staphylococcal infection. Finally, our bioinformatic analysis leads to a classification of temporins into six types and confers significance to this NMR structure since temporin-1OLa shares a sequence model with 62% of temporins. Collectively, our results indicate the potential of temporin-1OLa as a new anti-MRSA compound, which shows an even better anti-biofilm capability in combination with linezolid. |
| Databáze: | OpenAIRE |
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