Pyrvinium: A Novel Antifungal Agent with Unique ROS-Dependent Autophagy Induction in Candida albicans

Overview

Azole antifungals have long served as frontline therapies for Candida infections due to their efficacy and oral bioavailability. However, the increasing prevalence of azole- resistant Candida species presents a significant clinical challenge which leads to urgent need for alternative anti-fungal strategies. My previous study demonstrated the significant anti-fungal effect of pyrvinium pamoate, an FDA-approved anthelmintic drug against Candida albicans, suggesting its potential as an alternative anti-fungal agent. However, the intracellular mechanisms underlying its anti-fungal effect remain poorly understood.The current study focuses on elucidating the cellular pathways that mediate pyrvinium pamoate-induced fungal cell death, with a particular emphasis on the role of autophagic processes in regulating fungal viability. Autophagy is a conserved eukaryotic stress-response pathway essential for cellular homeostasis and survival. In my previous study, pyrvinium pamoate was shown to inhibit C. albicans growth by inducing an acute autophagic response independent of nutrient starvation, suggesting activation of an alternative autophagy-inducing mechanism. One possible mechanism of acute autophagic induction is mediated through reactive oxygen species (ROS) generation. Based on these findings, I hypothesized that pyrvinium pamoate promotes ROS generation, which activates autophagic pathways that lead to compromised C. albicans viability. To test my hypothesis, I conducted comprehensive analyses of autophagy induction and quantitation, ROS production, mitochondrial activity, synergistic effect with rapamycin and cell viability with combination therapy with blue light using various biochemical and cellular assays. Autophagy induction was quantified and ROS production was observed using Cyto-ID Green staining, DCFDA staining and flow cytometry. Pyrvinium treatment resulted in 88.05% increase in autophagic activity within 15 minutes. Concurrently, intracellular ROS levels increased by 88.04% within the same time frame, indicating rapid oxidative stress induction. Mitochondrial levels were also assessed and found to be constantly elevated regardless of pyrvinium treatment, suggesting mitochondrial content or activity do not change in early response. In the pyrvinium-rapamycin spot assay, the combination treatment did not produce a significantly greater growth inhibition than pyrvinium alone, indicating no synergistic effect. In contrast, combination therapy with pyrvinium pamoate and blue light exposure led to a significantly greater reduction in C. albicans' viability compared to either treatment alone, demonstrating a synergistic anti- fungal effect based on ROS-mediated autophagy induction. Collectively, these results support my hypothesis in which pyrvinium pamoate induces acute, ROS-mediated autophagy in C. albicans, leading to excessive autophagic activation and subsequent cell death.

Competition history

• CSEF 2026 Microbiology (Senior Division) · Entry S-16-12

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