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Vesicle inhibition reduces Candida biofilm resistance

Summary

Researchers found that common FDA-approved drugs designed to block vesicle production in human cells can also reduce the protective matrix that Candida fungus builds around itself in biofilms. By combining these vesicle-blocking drugs with the antifungal fluconazole, the scientists were able to kill biofilm-forming Candida more effectively than either treatment alone. This discovery suggests a new approach to treating stubborn fungal infections on medical devices like catheters, potentially eliminating the need to surgically remove infected equipment.

Background

Candida albicans forms biofilms on medical devices that are highly resistant to antifungal drugs. The biofilm matrix is delivered to the extracellular space by vesicles where they deposit and confer drug resistance. Previous studies identified turbinmicin as an antifungal that inhibits fungal vesicular trafficking and enhances biofilm susceptibility to other antifungals.

Objective

To determine whether mammalian exosome production inhibitors can reduce Candida albicans extracellular vesicle production and eliminate biofilm matrix assembly, thereby rendering biofilms susceptible to fluconazole.

Results

All five mammalian vesicle inhibitors enhanced fluconazole efficacy against biofilms in vitro and in vivo. Treatment with these inhibitors reduced extracellular vesicle production by two- to fourfold and significantly reduced visible biofilm matrix. Addition of exogenous extracellular vesicles to inhibitor-treated biofilms partially restored drug resistance, confirming an EV-dependent mechanism.

Conclusion

Mammalian extracellular vesicle inhibitors can disrupt Candida biofilm matrix assembly and enhance antifungal susceptibility through reduction of vesicle-mediated matrix delivery. Vesicle trafficking pathways represent a promising therapeutic target for recalcitrant fungal biofilms, with potential clinical application via catheter lock therapy.
  • Published in:Antimicrobial Agents and Chemotherapy,
  • Study Type:Experimental Research,
  • Source: 10.1128/aac.00045-25, PMID: 40135881
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