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Updated: Jul 13, 2025
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Multi-arm ε-polylysines exhibit broad-spectrum antifungal activities against Candida species
Yuanqiao Cao1,2, Ming Liu1, Miaomiao Han1
1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, P. R. China. sji@ciac.ac.cn.
Abstract:
Invasive fungal infections pose a crucial threat to public health and are an under-recognized component of antimicrobial resistance, which is an emerging crisis worldwide. Here we designed and synthesized a panel of multi-arm ε-polylysines (ε-mPLs, nR-Km) with a precise number of n = 3-6 arms of ε-oligo(L-lysine)s and a precise arm length of m = 3-7 ε-lysine residues. ε-mPLs have good biocompatibility and exhibited broad-spectrum antifungal activities towards Aspergillus, Mucorales and Candida species, and their antifungal activities increased with residue arm length. Among these ε-mPLs, 3R-K7 showed high antifungal activity against C. albicans with a MIC value of as low as 24 μg mL-1 (only 1/16th that of ε-PL) and also exhibited similar antifungal activity towards the clinically isolated multi-drug resistant (MDR) C. albicans strain. Furthermore, 3R-K7 could inhibit the formation of C. albicans biofilms and kill the cells within mature C. albicans biofilms. Mechanistic studies proved that 3R-K7 killed fungal cells by entering the cells to generate reactive oxygen species (ROS) and induce cell apoptosis. An in vivo study showed that 3R-K7 significantly increased the survival rate of mice in a systemic murine candidiasis model, demonstrating that ε-mPL has great potential as a new antifungal agent.
Insights
New multi-arm ε-polylysines (ε-mPLs) show potent antifungal activity against resistant fungal strains. These compounds effectively combat invasive fungal infections and biofilms, offering promise as novel antimicrobial agents.
Area of Science:
- Biochemistry
- Antimicrobial Resistance
- Drug Discovery
Background:
- Invasive fungal infections are a significant public health threat and contribute to the global antimicrobial resistance crisis.
- Existing treatments face challenges due to emerging resistance and limited efficacy.
- Novel antifungal agents are urgently needed to combat resistant fungal pathogens.
Purpose of the Study:
- To design and synthesize multi-arm ε-polylysines (ε-mPLs) with controlled arm number and length.
- To evaluate the broad-spectrum antifungal activity and biocompatibility of ε-mPLs.
- To investigate the efficacy of ε-mPLs against drug-resistant fungal strains and biofilms, and elucidate their mechanism of action.
Main Methods:
- Synthesis of ε-mPLs with varying arm numbers (n=3-6) and arm lengths (m=3-7).
- Antifungal activity testing against Aspergillus, Mucorales, and Candida species, including multi-drug resistant strains.
- Biofilm inhibition and eradication assays.
- Mechanistic studies involving reactive oxygen species (ROS) generation and apoptosis induction.
- In vivo efficacy evaluation using a murine candidiasis model.
Main Results:
- ε-mPLs demonstrated broad-spectrum antifungal activity with efficacy increasing with arm length.
- 3R-K7 exhibited potent activity against Candida albicans (MIC=24 μg mL⁻¹), outperforming ε-PL, and was effective against multi-drug resistant strains.
- 3R-K7 inhibited biofilm formation and eradicated cells within mature biofilms.
- Mechanistic studies revealed ROS generation and apoptosis induction as the mode of cell death.
- In vivo studies showed 3R-K7 significantly improved survival rates in a murine candidiasis model.
Conclusions:
- Multi-arm ε-polylysines (ε-mPLs) represent a promising class of novel antifungal agents.
- 3R-K7 displays potent activity against Candida albicans, including resistant strains and biofilms.
- The compound's mechanism involves ROS generation and apoptosis, with demonstrated in vivo efficacy.
- ε-mPLs hold significant potential for development into new therapeutic strategies against invasive fungal infections.
