Octopromycin: Antibacterial and antibiofilm functions of a novel peptide derived from Octopus minor against multidrug-resistant Acinetobacter baumannii. Issue 117 (October 2021)

• Record Type: Journal Article
• Authors: Rajapaksha, D.C.; Jayathilaka, E.H.T. Thulshan; Edirisinghe, S.L.; Nikapitiya, Chamilani; Lee, Joeun; Whang, Ilson; De Zoysa, Mahanama
• Is Part Of: Fish & shellfish immunology. Issue 117(2021)
• Page Start: 82
• Page End: 94
• Publication Date: 2021-10
• Subjects: Acinetobacter baumannii -- Antibacterial -- Antibiofilm -- Octopromycin -- Octopus minor -- Zebrafish; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2021.07.019
• Languages: English
• ISSNs: 1050-4648

Abstract

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 mock-treated fish with PBS (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. Graphical abstract: Image 1 Highlights: Antimicrobial peptide "Octopromycin is derived from prolin rich protein from Octopus minor . Octopromycin displayed strong antibacterial activity against Acinetobacter baumannii . Octopromycin can inhibit and eradicate the biofilm associated with A. baumannii . A. baumannii infected zebrafish are protected by Octopromycin treatment.