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Published on: January 7, 2022
Scymicrosin7-26, a Scylla paramamosain-derived novel antimicrobial peptide, exhibits efficacy against
Cong Hu1, Fangyi Chen2,3,4, Ying Zhou2,3,4
1Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
Abstract:
The escalating misuse of antibiotics has precipitated a worldwide crisis of bacterial resistance, greatly complicating the clinical management of multidrug-resistant bacterial infections, which now present a profound threat and a growing burden on public health systems. This situation necessitates the development of innovative anti-infective therapeutics. This work focuses on Scymicrosin7-26, a newly identified antimicrobial peptide (AMP) sourced from the crustacean Scylla paramamosain. AMPs typically derived from crustaceans are often characterized by suboptimal potency, instability, potential toxicity, and a narrow spectrum of activity, whereas Scymicrosin7-26 exhibits certain improvements in these regards. It exhibited antibacterial activity against five types of common clinically isolated multidrug-resistant organisms (MDROs). It inhibited both the formation and maturation of biofilms in carbapenem-resistant Pseudomonas aeruginosa (CR-PA) as well as methicillin-resistant Staphylococcus aureus (MRSA) without readily inducing resistance. Scymicrosin7-26 retained stable antimicrobial activity under physiological salt conditions and showed no significant antagonism when combined with several conventional antibiotics. It also demonstrated low toxicity toward RAW264.7, HEK293T, and Beas-2B cell lines, as well as human erythrocytes. Using fluorescence and electron microscopy, we observed disruption of bacterial surface structures. DNA binding assays further indicated the peptide's capacity to interact with bacterial genomic DNA. Moreover, Scymicrosin7-26 alleviated lipopolysaccharide (LPS)-triggered inflammatory responses via concurrent blockade of MAPK and NF-κB pathway activation. With its antibacterial activity against multidrug-resistant pathogens, anti-inflammatory property, and safety profile, Scymicrosin7-26 exhibits therapeutic potential for managing infections caused by multidrug-resistant bacteria.
Insights
A novel antimicrobial peptide, Scymicrosin7-26, shows promise against multidrug-resistant bacteria and biofilms. This peptide also possesses anti-inflammatory properties and a favorable safety profile, offering potential for new infection treatments.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Antibiotic resistance is a global health crisis requiring novel therapeutics.
- Antimicrobial peptides (AMPs) are a potential alternative, but often face challenges like low potency and toxicity.
- Crustacean-derived AMPs typically show limitations, necessitating the search for improved candidates.
Purpose of the Study:
- To investigate the antibacterial activity, biofilm inhibition, and safety of Scymicrosin7-26, a novel AMP from Scylla paramamosain.
- To evaluate the therapeutic potential of Scymicrosin7-26 against multidrug-resistant organisms (MDROs) and its anti-inflammatory effects.
Main Methods:
- Antibacterial activity testing against five common MDROs.
- Biofilm formation and maturation inhibition assays using carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and methicillin-resistant Staphylococcus aureus (MRSA).
- Cell toxicity assays, DNA binding assays, and analysis of inflammatory pathway activation (MAPK, NF-κB).
Main Results:
- Scymicrosin7-26 demonstrated broad-spectrum activity against MDROs and inhibited biofilm formation/maturation without inducing resistance.
- The peptide showed stability in physiological conditions, no antagonism with conventional antibiotics, and low toxicity to host cells and erythrocytes.
- Microscopy revealed bacterial surface structure disruption, and DNA binding assays confirmed interaction with genomic DNA. LPS-induced inflammation was alleviated via MAPK and NF-κB pathway blockade.
Conclusions:
- Scymicrosin7-26 exhibits significant antibacterial efficacy against MDROs and potent biofilm inhibition.
- The peptide possesses a favorable safety profile and anti-inflammatory properties, suggesting its potential as a therapeutic agent.
- Scymicrosin7-26 represents a promising candidate for developing novel treatments against challenging bacterial infections.
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