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Updated: Sep 24, 2025
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function
Chao-Qin Sun1,2, Jian Peng1,3, Long-Bing Yang1
1The Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
Abstract:
Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.
Insights
A novel peptide, C18, demonstrates potent antifungal activity against Candida species, including drug-resistant strains. This peptide shows promise as a new therapeutic agent for candidiasis by disrupting fungal cell integrity and virulence.
Area of Science:
- Mycology
- Infectious Diseases
- Biochemistry
Background:
- Global fungal infections are rising, exacerbated by multidrug resistance, necessitating new treatment strategies.
- Candida albicans is a major opportunistic pathogen, particularly in immunocompromised individuals.
- Antimicrobial peptides (AMPs) offer potential as alternative antifungal agents.
Purpose of the Study:
- To evaluate the antifungal activity and mechanism of action of a modified Cecropin-4 peptide, C18, against Candida species.
- To assess C18's efficacy against fluconazole-resistant Candida tropicalis and its impact on Candida albicans virulence.
- To investigate C18's therapeutic potential in a Galleria mellonella infection model.
Main Methods:
- Minimum inhibitory concentration (MIC) assays were performed against various Candida species, including fluconazole-resistant isolates.
- In vitro studies assessed C18's killing kinetics compared to fluconazole and its effects on C. albicans virulence factors (cell structure, hyphae transition, biofilm formation).
- A Galleria mellonella infection model was used to evaluate C18's in vivo efficacy and survival rates. Mechanistic studies involved measuring reactive oxygen species (ROS), cytosolic Ca2+, mitochondrial membrane potential (ΔΨm), and ATP levels.
Main Results:
- C18 exhibited significant antifungal activity against Candida albicans and non-albicans Candida species, with MICs ranging from 4–32 μg/ml.
- C18 demonstrated high efficacy against fluconazole-resistant Candida tropicalis (MIC 8–16 μg/ml) and outperformed fluconazole in killing planktonic C. albicans.
- C18 attenuated C. albicans virulence by damaging cell structure, inhibiting hyphae transition and biofilm formation. In vivo, C18 improved Galleria mellonella survival rates by 70% and reduced fungal load.
- Mechanistically, C18 induced ROS generation and Ca2+ accumulation, leading to mitochondrial dysfunction, loss of mitochondrial membrane potential, and ATP depletion in C. albicans.
Conclusions:
- C18 is a potent antifungal agent effective against a range of Candida species, including drug-resistant strains.
- C18 exhibits a novel mechanism of action involving the induction of mitochondrial dysfunction via ROS and Ca2+.
- C18 presents a promising therapeutic candidate for treating candidiasis, warranting further development.
