How a bacterial molecule starves a drug-resistant fungus

Most people carry Candida albicans in their gut without ever knowing it. In its everyday yeast form, this fungus is a quiet, harmless member of the gut microbiome. But under the right conditions it can switch into a branching, thread-like form called hyphae that burrows into tissue, seeds infections, and in the worst cases gets into the bloodstream. With drug-resistant Candida infections becoming a bigger problem in hospitals worldwide, researchers have been hunting for anything that can push the fungus back toward its harmless state before it does damage. A new study out of Monash University and the University of Warwick has found a promising lead, hiding in the chemistry of another microbe entirely.

Key takeaways

• A bacterial molecule called gladiolin speeds up the switch of the gut fungus Candida albicans from its invasive, thread-like hyphae form back into harmless yeast cells.
• It works by hijacking the fungus's metabolism, forcing it to burn through its sugar supply faster, which shuts down a signaling pathway the fungus needs to stay in its aggressive form.
• This is a lab dish (in vitro) discovery using fungal cell cultures, not an animal or human trial, so it is not a treatment yet.
• The molecule also boosted the effect of an existing antifungal drug, amphotericin B, on lab-grown fungal biofilms, hinting at a possible future combination approach.

Gladiolin Forces Candida Albicans Back Into Its Harmless Yeast Form

Researchers found that a natural bacterial compound called gladiolin accelerates the return of Candida albicans from its invasive hyphae form to its harmless yeast form, publishing the mechanism behind it in Current Biology. Gladiolin is a polyketide (a class of chemical compound many bacteria make to fight off competitors), originally isolated from Burkholderia gladioli, a bacterium first found in the lungs of a patient with cystic fibrosis. The research team, led by Manasa Bharathwaj and senior author Ana Traven at Monash University's Biomedicine Discovery Institute, working with chemists at the University of Warwick, built a way to watch this switch happen in real time under a microscope. When they added gladiolin to hyphae-forming C. albicans, the fungus did not stop growing its invasive filaments right away, but it flipped back to yeast form faster: in quantified live-imaging experiments, the switch to yeast began at around 8 hours of growth with gladiolin present, compared to about 10 hours without it, after which yeast cells proliferated more quickly.

Drug-Resistant Candida Infections Are a Growing Hospital Threat

The population most affected by this kind of fungal shape-shifting is hospitalized and immunocompromised patients, where Candida species cause bloodstream infections known as candidemia. The U.S. Centers for Disease Control and Prevention estimates candidemia causes tens of thousands of infections a year in the United States alone, with in-hospital mortality commonly cited in the range of 25 to 50 percent depending on the patient population, and the World Health Organization named Candida albicans a critical-priority fungal pathogen in 2022 because so few new antifungal drugs are in development. The CDC also separately flags drug-resistant Candida species as a "serious" antimicrobial resistance threat. Anything that nudges the fungus away from its invasive hyphal form, without relying on the handful of existing antifungal drug classes, is of real interest to infection researchers because it opens up an entirely different angle of attack: targeting how the fungus behaves rather than trying to kill it outright.

Live-Cell Imaging Assay Tracked the Fungal Shape Switch in Real Time

The methodological move that makes this study convincing is a custom fluorescent reporter system the team engineered specifically to catch this transition as it happens. They inserted a glowing marker protein, dTomato, into the fungus's genome under the control of a gene promoter that only switches on in yeast cells, then filmed the fungus over many hours as it grew, elongated into hyphae, and reverted back. This let them quantify, rather than just eyeball, exactly when and how fast the transition occurred across repeated experiments. They also tested the effect on C. albicans isolates pulled from different infection sites, including the bloodstream and oral and vaginal mucosa, and found gladiolin sped up the yeast switch in strains capable of forming hyphae in the first place, while strains that barely filament to begin with were unaffected.

What Cutting Off Candida's Sugar Supply Means for Treatment

For a reader wondering what this means for their own gut health, the honest answer right now is: not much, directly, and nothing to act on yet. This is not a supplement, probiotic, or dietary change, and no one should interpret it as a reason to alter their diet or take a specific compound. What it does show is a genuinely new mechanism: gladiolin reprograms the fungus's metabolism, pushing it to consume glucose (a simple sugar) faster and build up more ergosterol (a lipid unique to fungal cell membranes and the target of several existing antifungal drugs). That faster sugar burn-through starves a signaling pathway called Ras-cAMP, a chemical messaging system the fungus relies on to sustain its invasive hyphal growth; when that pathway loses fuel, the fungus reverts to yeast. Two genes that switch on sugar-processing machinery, Tye7 and Gal4, were shown to drive this acceleration, while a separate gene, Upc2, that controls ergosterol production pushed in the opposite direction, helping keep cells in the elongated, invasive form. If this line of research eventually leads to therapies, it would likely be as an add-on to existing antifungal treatment rather than a standalone cure, so anyone dealing with recurrent or severe Candida infections should keep that conversation with a doctor grounded in currently available antifungal drugs, not an unproven future molecule.

Still an Early-Stage Lab Finding, Not a Tested Therapy

The clearest limitation here is stage: everything in this paper was done in fungal cell cultures in a lab, not in animals or people, so there is no evidence yet that gladiolin is safe, effective, or even deliverable as a drug in a living organism. The researchers also do not yet know whether gladiolin's sugar-starvation trick would hold up against fungus that is already established in tissue, as opposed to fungus grown fresh in a dish, or how the compound would behave inside a complex, competing gut microbial community. Because gladiolin is itself a bacterial toxin the fungus did not evolve alongside in a controlled way, resistance to it over time is also an open question the study does not address.

Next Steps: Testing Gladiolin Alongside Existing Antifungal Drugs

The team's own experiments point toward the next logical step: combination therapy. In lab-grown fungal biofilms, a dense, resistant film of Candida cells, gladiolin boosted the effect of amphotericin B, one of the older and more potent antifungal drugs still in clinical use. That synergy suggests gladiolin's real future utility might be as a partner drug that makes existing antifungals work harder, rather than a frontline treatment on its own. The obvious next steps, not yet reported, are testing gladiolin (or a safer derivative of it) in animal models of Candida infection, and confirming whether the sugar-starvation mechanism holds up against the drug-resistant clinical strains that worry hospitals most. The research was funded by the Australian Research Council, Australia's National Health and Medical Research Council, and the universities involved, with no pharmaceutical industry funding disclosed.

Common Questions

Is gladiolin a new antifungal drug I could take? No. This is a lab-based mechanism discovery in fungal cell cultures. It has not been tested in animals or people and is not an approved or available treatment.

Does this mean Candida albicans in my gut is dangerous? No. Most people carry C. albicans in their gut as a harmless yeast-form resident for their entire lives. This research is about the small subset of cases where it switches into its invasive hyphal form and causes infection, particularly in hospitalized or immunocompromised patients.

Could this replace existing antifungal drugs like amphotericin B? Not based on this study. The researchers found gladiolin worked alongside amphotericin B rather than replacing it, suggesting any future use would likely be as a combination treatment.

References

1. Manasa Bharathwaj, Vinzenz Hofferek, Angavai Swaminathan, et al. (2026). A bacterial metabolite rewires fungal metabolism, triggering the hyphae-to-yeast transition. Current Biology. https://doi.org/10.1016/j.cub.2026.07.057
2. CDC Antibiotic Resistance Threats Report — Drug-resistant Candida. cdc.gov. https://www.cdc.gov/antimicrobial-resistance/media/pdfs/candida-508.pdf