Avaliação da influência dos agroquímicos mancozeb e carbendazim na susceptibilidade de Candida glabrata, Cryptococcus gattii e Cryptococcus neoformans aos antifúngicos clínicos

Abstract

Cryptococcus gattii, Cryptococcus neoformans and Candida glabrata are yeasts that occur in the environment and have already been isolated from various plantations. As they occur in the soil, these fungi are exposed to agrochemicals, which can exert selection pressure on these fungi and induce resistance. In this context, the aim of this work was to evaluate the influence of the agrochemicals mancozeb and carbendazim on the susceptibility to clinical antifungals and virulence factors of strains of C. gattii¸ C. neoformans and C. glabrata. To evaluate the impact of the agrochemicals on the selected strains, they were exposed to increasing concentrations of the agricultural antifungal agents until growth ceased, a process referred to here as adaptation. The test was carried out at 30°C and 35°C. The strains adapted to 30°C were able to tolerate higher concentrations of the agrochemical, showing that temperature is an important factor in this process. After the adaptation phase, the minimum inhibitory concentration for clinical antifungals of these strains exposed to the agrochemical (adapted) was evaluated in comparison to non-exposed strains (non-adapted). Reduced susceptibility to fluconazole and/or 5-flucytosine was observed in some adapted strains, indicating that there is cross-resistance between agrochemicals and clinical antifungals. Some strains remained resistant to FCZ and/or 5-FC after successive passages in agrochemical-free medium, indicating permanent cross-resistance, while others returned to their original susceptibility after cessation of exposure to the agrochemical, indicating transient cross- resistance. Mancozeb and carbendazim also altered the morphology of Cryptococcus strains, with a reduction in capsule size and the carbendazim-adapted strain C. gattii R265 forming pseudohyphae. When evaluating the effect of agrochemicals on biofilm formation, it was found that only the C. glabrata strains suffered changes in their ability to form biofilms. These results support the idea that the use of agrochemicals can significantly affect human pathogens present in the environment and impair their resistance to antifungal agents used in clinical practice. This interrelationship between human health and the environment underlines the need for a “One Health” approach to combat the increasing resistance to fungi observed in recent years.