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Published on: December 2, 2022
A Novel Antimicrobial Peptide Sparamosin26-54 From the Mud Crab Scylla paramamosain Showing Potent Antifungal
Yan-Chao Chen1, Ying Yang1, Chang Zhang1
1State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.
Abstract:
Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1-25 and Sparamosin26-54) were determined. The results showed that Sparamosin26-54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26-54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26-54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26-54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26-54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26-54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.
Insights
A novel antimicrobial peptide, Sparamosin26-54, effectively kills drug-resistant fungi like Cryptococcus neoformans by disrupting cell membranes and walls. This peptide shows potent anti-biofilm activity without harming mammalian cells, offering a promising new antifungal treatment.
Area of Science:
- Marine biotechnology
- Antimicrobial peptide discovery
- Fungal infection treatment
Background:
- Rising drug-resistant fungal infections necessitate novel therapeutic strategies.
- Current antifungal treatments have limitations.
- Antimicrobial peptides (AMPs) are a potential source for new drugs.
Purpose of the Study:
- To identify and characterize novel antimicrobial peptides from marine organisms.
- To evaluate the efficacy and mechanism of action of a newly identified peptide, Sparamosin, against pathogenic fungi, particularly Cryptococcus neoformans.
Main Methods:
- Identification and synthesis of Sparamosin and its truncated forms.
- Antimicrobial activity assays against various bacteria and fungi.
- Fungicidal kinetics, anti-biofilm assays, cytotoxicity tests, RNA sequencing, and mechanistic studies (cell membrane/wall integrity, ROS, MMP, DNA fragmentation).
Main Results:
- Sparamosin26-54 demonstrated potent activity against Gram-negative bacteria, Gram-positive bacteria, and fungi, including rapid killing of Cryptococcus neoformans.
- Sparamosin26-54 exhibited strong anti-biofilm activity against C. neoformans and showed no cytotoxicity to mammalian cells.
- Mechanistic studies revealed disruption of cell wall and membrane integrity, increased reactive oxygen species, disrupted mitochondrial membrane potential, and induced DNA fragmentation, leading to apoptosis.
Conclusions:
- Sparamosin26-54 is a promising antimicrobial agent with significant potential for treating fungal infections, especially those caused by Cryptococcus neoformans.
- Its unique mechanism of action, targeting cell wall and membrane integrity, offers a novel approach to combatting antifungal drug resistance.
