In recent years, the demand for new antifungal drugs has increased, in part due to the rise of antifungal drug resistance as well as the emergence of new pathogenic species such as Candida auris. Previous research has shown that Candida albicans is hypersensitive to copper (Cu) dyshomeostasis both in the presence and absence of antifungal drug treatment by the popular triazole drug fluconazole. To further attenuate this response, we have investigated the ability of ammonium tetrathiomolybdate (TTM) to alter metal homeostasis in C. albicans. We have found that this common Cu chelator itself has some antifungal properties but more importantly interferes with the metalloproteome, altering stability of metalated proteins such as cytochrome b, superoxide dismutase and the multicopper oxidase Fet31. These results indicate that TTM has the ability to interfere with metal-based cellular processes and alter antifungal drug response.

Ammonium tetrathiomolybdate’s impact on Candida albicans

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