| Autor: |
Bastos, Rafael Wesley1 (AUTHOR), Freitas, Gustavo José Cota1 (AUTHOR), Carneiro, Hellem Cristina Silva1 (AUTHOR), Oliveira, Lorena Vívien Neves1 (AUTHOR), Gouveia-Eufrasio, Ludmila1 (AUTHOR), Santos, Anderson Philip Nonato1 (AUTHOR), Moyrand, Frédérique1 (AUTHOR), Maufrais, Corinne1 (AUTHOR), Janbon, Guilhem1 (AUTHOR), Santos, Daniel Assis1 (AUTHOR) das@ufmg.br |
| Zdroj: |
Science of the Total Environment. Sep2019, Vol. 681, p516-523. 8p. |
| Abstrakt: |
Agrochemicals such as the non-azoles, used to improve crop productivity, poses severe undesirable effects on the environment and human health. In addition, they induce cross-resistance (CR) with clinical drugs in pathogenic fungi. However, till date emphasis has been given to the role of azoles on the induction of CR. Herein, we analyzed the effect of a non-azole agrochemical, pyraclostrobin (PCT), on the antifungal susceptibility and virulence of the human and animal pathogens Cryptococcus gattii and C. neoformans. We determined the minimum inhibitory concentration (MIC) of fluconazole (FLC), itraconazole, ravuconazole, amphotericin B, and PCT on colonies: (i) that were not exposed to PCT (non-adapted-NA-cultures), (ii) were exposed at the maximum concentration of PCT (adapted-A-cultures) and (iii) the adapted colonies after cultivation 10 times in PCT-free media (10 passages-10p–cultures). Our results showed that exposure to PCT induced both temporary and permanent CR to clinical azoles in a temperature-dependent manner. With the objective to understand the mechanism of induction of CR through non-azoles, the transcriptomes of NA and 10p cells from C. gattii R265 were analyzed. The transcriptomic analysis showed that expression of the efflux-pump genes (AFR1 and MDR1) and PCT target was higher in resistant 10p cells than that in NA. Moreover, the virulence of 10p cells was reduced as compared to NA cells in mice, as observed by the differential gene expression analysis of genes related to ion-metabolism. Additionally, we observed that FLC could not increase the survival rate of mice infected with 10p cells, confirming the occurrence of permanent CR in vivo. The findings of the present study demonstrate that the non-azole agrochemical PCT can induce permanent CR to clinical antifungals through increased expression of efflux pump genes in resistant cells and that such phenomenon also manifests in vivo. Unlabelled Image • Exposure to pyraclostrobin induces cross-resistance with clinical antifungals in Cryptococcus • Non-azole agrochemical exposure increases expression of efflux pumps in C. gattii. • Pyraclostrobin-exposed yeasts are less virulent than non-exposed ones in mice. • Fluconazole is not able to treat cryptococcosis by pyraclostrobin-exposed cells. • Agrochemicals jeopardize animal and human health by influencing fungal resistance. [ABSTRACT FROM AUTHOR] |
| Databáze: |
GreenFILE |
| Externí odkaz: |
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Full Text from ScienceDirect