The chemical control of pests and weeds is employed to improve crop production and the quality of agricultural products. The intensive use of pesticides, however, may cause environmental contamination, thus altering microbial communities. Cryptococcus gattii is an environmental yeast and the causative agent of cryptococcosis in both humans and animals. Up to this day, the effects of agrochemicals on human pathogens living in nature are still widely unknown. In this work, we analyzed the susceptibility of C. gattii to nonfungicide agrochemicals (herbicides and insecticides). Microdilution and drug-combination susceptibility tests were performed for the herbicides flumioxazin (FLX), glyphosate (GLY), isoxaflutole (ISO), pendimethalin (PEND), and also for the insecticide fipronil (FIP). Moreover, these compounds were combined with the clinical antifungals amphotericin B and fluconazole. The MIC values found for the agrochemicals were the following: < 16 μg/ml, for flumioxazin; 128 to 256 μg/ml, for FIP, ISO, and PEND; and >256 μg/ml, for GLY. Synergistic and antagonistic interactions, depending on the strain and concentration tested, were also observed. All strains had undergone adaptation to increasing levels of agrochemicals, in order to select the less susceptible subpopulations. During this process, one C. gattii strain (196 L/03) tolerated high concentrations (50 to 900 μg/ml) of all pesticides assessed. Subsequently, the strain adapted to flumioxazin, isoxaflutole and pendimethalin showed a reduction in the susceptibility to agrochemicals and clinical antifungals, suggesting the occurrence of cross-resistance. Our data point to the risk of exposing C. gattii to agrochemicals existing in the environment, once it might impact the susceptibility of clinical antifungals.

中文翻译：

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非抗真菌农药对致病真菌加氏隐球菌的影响。

对害虫和杂草进行化学控制可改善作物产量和农产品质量。但是，大量使用农药可能会造成环境污染，从而改变微生物群落。加蒂隐球菌是一种环境酵母，是人类和动物中隐球菌的病原体。直到今天，农用化学品对生活在自然界中的人类病原体的影响仍是未知之数。在这项工作中，我们分析了加迪梭菌对非杀真菌剂农药（除草剂和杀虫剂）的敏感性。对除草剂氟米沙星（FLX），草甘膦（GLY），异恶磷谷（ISO），二甲戊乐灵（PEND）以及杀虫剂氟虫腈（FIP）进行了微稀释和药物结合敏感性测试。此外，这些化合物与临床抗真菌药两性霉素B和氟康唑合用。农药的MIC值如下：氟米沙星<16μg/ ml；FIP，ISO和PEND为128至256μg/ ml; 对于GLY，> 256μg/ ml。还观察到协同作用和拮抗作用，这取决于所测试的菌株和浓度。为了选择不易感染的亚群，所有菌株都适应了增加水平的农用化学品。在此过程中，一株加蒂梭菌（196 L / 03）耐受所有评估的农药的高浓度（50至900μg/ ml）。随后，适应氟米沙星，异恶草环和二甲戊乐灵的菌株显示出对农用化学品和临床抗真菌药的敏感性降低，表明发生了交叉耐药。