Antibiotic Disarms Candida by Reversing Its Invasive Growth

Researchers from Monash University, in collaboration with the University of Warwick, have discovered how the bacterial antibiotic gladiolin can disarm Candida albicans, one of the leading causes of life-threatening fungal infections, opening new avenues for developing treatments. Published in Current Biology, the discovery is the latest outcome from the Monash Warwick Alliance Programme in Antimicrobial Resistance (AMR).

Led by researchers from the Monash Biomedicine Discovery Institute, the study reveals that gladiolin can switch Candida albicans from its tissue-damaging, invasive “hyphae” form back into its benign, round yeast form. Lead author Ana Traven said that although gladiolin was discovered several years ago as an antibiotic made by bacteria, its activity against fungal pathogens had remained poorly understood.

“The thread-like hyphae of Candida albicans allow the fungus to penetrate and damage human tissue and form drug-resistant biofilms, leading to dangerous infections,” Professor Traven said. “We’ve discovered gladiolin effectively ‘switches off’ this aggressive behavior, pushing the fungus back into its less harmful ‘yeast’ state. This gives us a different way to think about controlling fungal infections, not just by killing the fungus, but by disarming it.”

First author Manasa Bharathwaj added that gladiolin has a very interesting property, whereby it changes the metabolism of Candida albicans, inducing the pathogen to consume more glucose in its environment. “Since glucose is important for the invasive hyphae to grow, gladiolin tricks Candida to use up its glucose supply more quickly, forcing it to switch back to its less invasive yeast state,” Bharathwaj said.

The study builds on a 2024 discovery led by Professor Traven, Mibel Aguilar, and Greg Challis, which showed that gladiolin dramatically boosts the effectiveness of amphotericin B, one of the world’s most important antifungal medicines. Together, the two studies show that bacterial molecules like gladiolin can tackle dangerous fungi in multiple ways, both by boosting existing antifungal drugs and by switching off one of the fungus’s key disease-causing behavious.

“Importantly, our findings suggest that gladiolin could help existing drugs kill dangerous fungal pathogens, including drug-resistant biofilms that can form on medical devices, while potentially allowing lower, less toxic doses of antifungal drugs to be used,” Professor Challis said.

While Candida albicans normally lives harmlessly in the human body, it can cause life-threatening infections in critically ill or immunocompromised patients, particularly when it grows on medical devices such as catheters. “Fungal infections kill an estimated two million people worldwide each year, yet treatment options remain limited,” Professor Traven said. “There are no vaccines for fungal infections, and some of the antifungal medicines we do have can be highly toxic, highlighting the urgent need for new ways to prevent and treat these diseases.”