Bacterial compound gladiolin forces deadly fungus into harmless form

Scientists from Monash University and the University of Warwick have discovered how the bacterial antibiotic gladiolin disarms Candida albicans, a leading cause of life-threatening fungal infections. Published in Current Biology, the study shows that gladiolin forces the fungus to shift from its tissue-damaging, thread-like hyphae form back into its harmless, round yeast form.

Candida albicans normally lives harmlessly in the human body but can cause deadly infections in immunocompromised patients, especially when it forms drug-resistant biofilms on medical devices. The hyphae form allows the fungus to penetrate tissue and establish these persistent infections.

Lead author Professor Ana Traven of the Monash Biomedicine Discovery Institute said gladiolin was discovered years ago as a bacterial antibiotic, but its activity against fungal pathogens was poorly understood. The research reveals that gladiolin changes the fungus's metabolism, causing it to consume glucose more rapidly.

First author Dr. Manasa Bharathwaj explained that because glucose is essential for hyphae growth, this accelerated consumption starves the invasive form and forces a return to the yeast state. This "disarming" approach differs from traditional antifungals that aim to kill the pathogen outright.

The study also found that gladiolin dramatically increases the effectiveness of amphotericin B, one of the most important existing antifungal drugs. The combination could allow lower, less toxic doses of amphotericin B while still killing drug-resistant biofilms on medical devices.

Professor Greg Challis, co-director of the Monash Warwick Alliance Programme in Antimicrobial Resistance, said the findings illustrate how interdisciplinary collaboration can open new approaches to antimicrobial resistance. Fungal infections kill an estimated two million people worldwide each year, and treatment options remain limited.

The research builds on a 2024 discovery by the same team and adds to work from the Monash Warwick Alliance, which brings together the two universities to tackle antimicrobial resistance. The scientists are exploring whether naturally occurring bacterial molecules like gladiolin can inspire new treatments, following the same principle that led to penicillin.