Fenbendazole Controls <i>In Vitro</i> Growth, Virulence Potential, and Animal Infection in the <i>Cryptococcus</i> Model
Haroldo César de Oliveira, Luna S. Joffe, Karina Smidt Simon, Rafael F. Castelli, Flavia C. G. Reis, Arielle M. Bryan, Beatriz S. Borges, Lia Carolina Soares Medeiros, Anamélia Lorenzetti Bocca, Maurizio Del Poeta, Márcio L. Rodrigues
Abstract
at a low concentration. The mechanism of anticryptococcal activity of fenbendazole involved microtubule disorganization, as previously described for human parasites. In combination with fenbendazole, the concentrations of the standard antifungal amphotericin B required to control cryptococcal growth were lower than those required when this antifungal was used alone. Fenbendazole was not toxic to mammalian cells. During macrophage infection, the anticryptococcal effects of fenbendazole included inhibition of intracellular proliferation rates and reduced phagocytic escape through vomocytosis. Fenbendazole deeply affected the cryptococcal capsule. In a mouse model of cryptococcosis, the efficacy of fenbendazole to control animal mortality was similar to that observed for amphotericin B. These results indicate that fenbendazole is a promising candidate for the future development of an efficient and affordable therapeutic tool to combat cryptococcosis.