PUBLICATION
Octopromycin: Antibacterial and antibiofilm functions of a novel peptide derived from Octopus minor against multidrug-resistant Acinetobacter baumannii
- Authors
- Rajapaksha, D.C., Jayathilaka, E.H.T.T., Edirisinghe, S.L., Nikapitiya, C., Lee, J., Whang, I., De Zoysa, M.
- ID
- ZDB-PUB-210728-41
- Date
- 2021
- Source
- Fish & shellfish immunology 117: 82-94 (Journal)
- Registered Authors
- Keywords
- Acinetobacter baumannii, Antibacterial, Antibiofilm, Octopromycin, Octopus minor, Zebrafish
- MeSH Terms
-
- Acinetobacter Infections/drug therapy*
- Acinetobacter Infections/pathology
- Acinetobacter Infections/veterinary
- Acinetobacter baumannii/drug effects
- Acinetobacter baumannii/growth & development
- Acinetobacter baumannii/physiology
- Animals
- Anti-Bacterial Agents/pharmacology
- Anti-Bacterial Agents/therapeutic use*
- Antimicrobial Cationic Peptides/pharmacology
- Antimicrobial Cationic Peptides/therapeutic use*
- Biofilms/drug effects
- Cell Survival/drug effects
- Drug Resistance, Multiple, Bacterial/drug effects
- Embryo, Nonmammalian
- Erythrocytes/drug effects
- Fish Diseases/drug therapy*
- Fish Diseases/pathology
- HEK293 Cells
- Humans
- Kidney/drug effects
- Kidney/pathology
- Mice
- Octopodiformes*
- RAW 264.7 Cells
- Zebrafish
- PubMed
- 34311097 Full text @ Fish Shellfish Immunol.
Citation
Rajapaksha, D.C., Jayathilaka, E.H.T.T., Edirisinghe, S.L., Nikapitiya, C., Lee, J., Whang, I., De Zoysa, M. (2021) Octopromycin: Antibacterial and antibiofilm functions of a novel peptide derived from Octopus minor against multidrug-resistant Acinetobacter baumannii. Fish & shellfish immunology. 117:82-94.
Abstract
The emergence of carbapenem-resistant Acinetobacter baumannii has increased the risk of nosocomial infections, which pose a huge health threat. There is an urgent need to develop alternative therapies, including broad-spectrum antimicrobial peptides. In this study, we designed, characterized, and studied the antibacterial, antibiofilm effects and possible mode of actions of a novel synthetic peptide Octopromycin, derived from the proline-rich protein 5 of Octopus minor. Octopromycin consists of 38 amino acids, (+5) net positive charge, high hydrophobic residue ratio (36%), and two α-helix secondary structures. The minimum inhibitory concentration and minimum bactericidal concentration against A. baumannii were 50 and 200 μg/mL, respectively. Time-kill kinetics and bacterial viability assays confirmed the concentration-dependent antibacterial activity of Octopromycin. Field emission scanning electron microscopy images clearly showed ultrastructural alterations in Octopromycin-treated A. baumannii cells. Propidium iodide penetrated into Octopromycin-treated A. baumannii cells, demonstrating the loss of cell membrane integrity. Octopromycin treatment increased the production of reactive oxygen species in a concentration-dependent manner, and it inhibited the biofilm formation and showed biofilm eradication activity against A. baumannii. In vitro and in vivo safety evaluation revealed that Octopromycin was nontoxic to HEK293T and Raw 264.7 cells (<400 μg/mL), as well as mice red blood cells (<300 μg/mL), and zebrafish embryos (<4 μg/mL). An in vivo study results revealed that the A. baumannii-infected fish treated with Octopromycin exhibited a significantly higher relative percent survival (37.5%) than the infected fish mock-treated with PBS untreated group (16.6%). Furthermore, a decreased bacterial load and fewer alterations in histological analysis confirmed the successful control of A. baumannii by Octopromycin in vivo. Collectively, the results indicate that the antibacterial peptide Octopromycin may achieve rapid control of A. baumannii through multi-target interactions; it presents a desirable therapeutic option for the prevention and control of the infections.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping