The herbicide paraquat alters growth and melanin production on the Cryptococcus neoformans/Cryptococcus gattii species complex

Abstract

Paraquat (PQ) is a free-radical producing herbicide that affects cell membranes and can upset the environmental balance of microorganisms present in soil, such as Cryptococcus spp. This study aimed to evaluate the in vitro activity of PQ against Cryptococcus spp. in planktonic and biofilm forms, as well as the protective effect of antioxidant agents against the antifungal effect of PQ and the kinetics of melanin production in response to PQ. Susceptibility to PQ was evaluated by the microdilution. Cryptococcus sp. strains exposed to PQ were grown in media with ascorbic acid (AA) and glutathione (GSH). Melanin production was assessed in the presence of L-dopa + PQ. The minimum inhibitory concentration (MIC) of PQ against Cryptococcus spp. ranged from 8 -256 μg/mL. Furthermore, PQ reduced biofilm formation. AA and GSH restored the fungal growth of Cryptococcus spp. exposed to PQ. In addition, L-dopa + PQ delayed melanin production by 24 and 48 hours for C. deuterogattii and C. neoformans sensu lato, respectively, suggesting that PQ induces a fitness trade off in melanin production. Taken together, our data suggest that antifungal effect of PQ against Cryptococcus spp. exerts a possibly selective pressures interfering with biofilm formation and melanin production by these yeasts.