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Updated: Feb 9, 2026
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics
Michael R Yeaman1,2,3,4, Sabrina Büttner5,6, Karin Thevissen7
1Division of Molecular Medicine, Los Angeles County Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Abstract:
The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist existing treatment and cause severe illness has underscored the threat of drug-resistant fungal infections. To meet these growing challenges, mechanistically novel agents and strategies are needed that surpass the conventional fungistatic or fungicidal drug actions. Host defense peptides have long been misunderstood as indiscriminant membrane detergents. However, evidence gathered over the past decade clearly points to their sophisticated and selective mechanisms of action, including exploiting regulated cell death pathways of their target pathogens. Such peptides perturb transmembrane potential and mitochondrial energetics, inducing phosphatidylserine accessibility and metacaspase activation in fungi. These mechanisms are often multimodal, affording target pathogens fewer resistance options as compared to traditional small molecule drugs. Here, recent advances in the field are examined regarding regulated cell death subroutines as potential therapeutic targets for innovative anti-infective peptides against pathogenic fungi. Furthering knowledge of protective host defense peptide interactions with target pathogens is key to advancing and applying novel prophylactic and therapeutic countermeasures to fungal resistance and pathogenesis.
Insights
Host defense peptides offer novel strategies against drug-resistant fungal infections by targeting regulated cell death pathways. These peptides provide a promising alternative to conventional antibiotics for combating challenging pathogens like Candida auris.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Drug-resistant fungal infections, including Candida auris and invasive molds, pose a significant global health threat.
- Conventional antifungal agents face limitations due to emerging resistance, necessitating novel therapeutic approaches.
- Host defense peptides (HDPs) are increasingly recognized for their sophisticated mechanisms beyond simple membrane disruption.
Purpose of the Study:
- To explore the potential of regulated cell death (RCD) pathways as therapeutic targets for anti-fungal agents.
- To review recent advancements in understanding HDPs' mechanisms of action against pathogenic fungi.
- To highlight the role of HDPs in overcoming antifungal drug resistance.
Main Methods:
- Examination of existing literature on HDPs and their interactions with fungal pathogens.
- Analysis of HDP-induced fungal cell death mechanisms, including effects on transmembrane potential and mitochondrial energetics.
- Investigation of phosphatidylserine exposure and metacaspase activation as RCD indicators.
Main Results:
- HDPs exhibit selective and multimodal mechanisms of action against fungi, unlike conventional drugs.
- HDPs can perturb fungal transmembrane potential and mitochondrial function.
- HDPs induce key events in regulated cell death, such as phosphatidylserine accessibility and metacaspase activation.
Conclusions:
- Regulated cell death subroutines represent promising therapeutic targets for novel anti-fungal peptide development.
- Understanding HDP-pathogen interactions is crucial for developing effective countermeasures against fungal resistance.
- Innovative anti-infective peptides targeting RCD offer a new frontier in combating pathogenic fungi.
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