Proteomics to uncover new actors in the antifungal action of metformin. Impact on virulence traits, oxidative stress, and essential proteins from Candida albicans.

Metformin, a commonly prescribed medication, exhibits an unexplored ability to impact the biology of Candida albicans, as revealed by a recent study utilizing differential proteomics. This drug, known for its safety profile and anti-Candida properties, was found to inhibit the growth of C. albicans SC5314 in a dose-dependent manner.

This effect was amplified under low glucose conditions and filament-inducing environments. Moreover, metformin reduced virulence traits such as filamentation, biofilm formation, and invasive growth in the fungus.

The study also demonstrated that metformin induces oxidative stress, which can be neutralized by antioxidant agents like N-acetylcysteine and glutathione. Notably, at a concentration of 50 mM, metformin significantly enhanced the efficacy of fluconazole under low glucose conditions. Upon exposure to metformin, 1,899 proteins were identified and quantified in C. albicans SC5314. Of these, 95 proteins were found to be upregulated, while 47 were downregulated.

The downregulated proteins, specifically 26 encoded by essential genes, underscore the profound impact of metformin on C. albicans viability. The study's Gene Ontology analysis revealed that the most affected functions were ATP binding, inhibition of ATPase activity, translation inhibition, mitochondrial function, filamentation, and responses to oxidative stress and antifungals. These findings suggest that metformin significantly compromises both the viability and virulence of C. albicans at high concentrations.

Given that high concentrations of metformin have been detected in the intestinal tract and are common in immunocompromised patients, including those undergoing chemotherapy or post-surgery, understanding the anti-Candida action of metformin becomes increasingly relevant.