DP1, a multifaceted synthetic peptide: Mechanism of action, activity and clinical potential.
Autor: | Maan M; Department of Biophysics, Panjab University, Chandigarh, U.T. 160014, India., Goyal H; Department of Biophysics, Panjab University, Chandigarh, U.T. 160014, India., Joshi S; Department of Biophysics, Panjab University, Chandigarh, U.T. 160014, India., Barman P; Institute of Forensic Science and Criminology (UIEAST), Panjab University, Chandigarh, U.T. 160014, India., Sharma S; Department of Biophysics, Panjab University, Chandigarh, U.T. 160014, India., Kumar R; Department of Physics, Panjab University, Chandigarh, U.T. 160014, India., Saini A; Department of Biophysics, Panjab University, Chandigarh, U.T. 160014, India. Electronic address: avneet@pu.ac.in. |
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Jazyk: | angličtina |
Zdroj: | Life sciences [Life Sci] 2024 Mar 01; Vol. 340, pp. 122458. Date of Electronic Publication: 2024 Jan 23. |
DOI: | 10.1016/j.lfs.2024.122458 |
Abstrakt: | Aims: Microbial infections remain a leading cause of mortality worldwide, with Staphylococcus aureus (S. aureus) being a prominent etiological agent, responsible for causing persistent bacterial infections in humans. It is a nosocomial, opportunistic pathogen, capable to propagate within the bloodstream and withstand therapeutic interventions. In the current study, a novel, indigenously designed synthetic antimicrobial peptide (sAMP) has been evaluated for its antimicrobial potential to inhibit the growth and proliferation of S. aureus. Main Methods: The sAMP, designed peptide (DP1) was evaluated for its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of pathogenic bacterial strains. Membrane mechanistic studies were performed by measuring membrane conductivity via dielectric spectroscopy and visualizing changes in bacterial membrane structure through field emission scanning electron microscopy (FE-SEM). Further, DP1 was tested for its in vivo antimicrobial potential in an S. aureus-induced systemic infection model. Key Findings: The results indicated that DP1 has the potential to inhibit the growth and proliferation of a broad spectrum of Gram-positive, Gram-negative and multidrug-resistant (MDR) bacterial strains. Strong bactericidal effect attributed to change in electrical conductivity of the bacterial cells leading to membrane disruption was observed through dielectric spectroscopy and FE-SEM micrographs. Further, in the in vivo murine systemic infection study, 50 % reduction in S. aureus bioburden was observed within 1 day of the administration of DP1. Significance: The results indicate that DP1 is a multifaceted peptide with potent bactericidal, antioxidant and therapeutic properties. It holds significance as a novel drug candidate to effectively combat S. aureus-mediated systemic infections. Competing Interests: Declaration of competing interest The authors of the manuscript declare that they do not have any conflict of interest. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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