Novel Arginine- and Proline-Rich Candidacidal Peptides Obtained through a Bioinformatic Approach
Tecla Ciociola1, Laura Giovati1, Tiziano De Simone1
1Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Abstract:
Antimicrobial resistance is a major public health concern worldwide. Albeit to a lesser extent than bacteria, fungi are also becoming increasingly resistant to antifungal drugs. Moreover, due to the small number of antifungal classes, therapy options are limited, complicating the clinical management of mycoses. In this view, antimicrobial peptides (AMPs) are a potential alternative to conventional drugs. Among these, Proline-rich antimicrobial peptides (PrAMPs), almost exclusively of animal origins, are of particular interest due to their peculiar mode of action. In this study, a search for new arginine- and proline-rich peptides from plants has been carried out with a bioinformatic approach by sequence alignment and antimicrobial prediction tools. Two peptide candidates were tested against planktonic cells and biofilms of Candida albicans and Candida glabrata strains, including resistant isolates. These peptides showed similar potent activity, with half-maximal effective concentration values in the micromolar range. In addition, some structural and functional features, revealing peculiar mechanistic behaviors, were investigated.
Insights
New plant-derived antimicrobial peptides show potent activity against drug-resistant fungi like Candida. These proline-rich peptides offer a promising alternative to conventional antifungal therapies, addressing a critical global health challenge.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Antimicrobial resistance, particularly antifungal resistance, is a growing global public health threat.
- Limited antifungal drug classes and increasing resistance necessitate the development of novel therapeutic strategies.
- Antimicrobial peptides (AMPs), especially Proline-rich antimicrobial peptides (PrAMPs), present a potential alternative to conventional antifungals due to their unique mechanisms.
Purpose of the Study:
- To identify novel plant-derived arginine- and proline-rich peptides with potential antifungal activity.
- To evaluate the efficacy of identified peptide candidates against planktonic and biofilm forms of pathogenic fungi, including resistant strains.
- To investigate the structural and functional characteristics of these novel peptides.
Main Methods:
- Bioinformatic analysis including sequence alignment and antimicrobial prediction tools for peptide discovery.
- In vitro testing of peptide candidates against planktonic cells and biofilms of *Candida albicans* and *Candida glabrata*.
- Determination of half-maximal effective concentration (EC50) values and investigation of structural/functional properties.
Main Results:
- Two plant-derived peptide candidates demonstrated potent antimicrobial activity against *Candida* species, including resistant isolates.
- Effective concentrations were in the micromolar range, indicating significant potency.
- Preliminary investigations revealed unique mechanistic behaviors and structural features of the tested peptides.
Conclusions:
- Plant-derived proline-rich peptides are a promising source for novel antifungal agents.
- These peptides exhibit potent activity against clinically relevant and resistant fungal strains.
- Further research into their mechanisms could lead to new therapeutic strategies against mycoses.
