From the environment to the host: How non-azole agrochemical exposure affects the antifungal susceptibility and virulence of Cryptococcus gattii

Bastos, Rafael Wesley; Freitas, Gustavo José Cota de; Carneiro, Hellem Cristina Silva; Oliveira, Lorena; Gouveia-Eufrásio, Ludmila; Santos, Anderson Philip Nonato; Moyrand, Frédérique; Maufrais, Corinne; Janbon, Guilhem; Santos, Danielle Anjos dos

doi:10.1016/j.scitotenv.2019.05.094

Cited by 22 publications

(21 citation statements)

References 40 publications

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“…The exposure to agrochemicals caused cross-resistance to medical azoles, remarkably fluconazole. The cross-resistance was permanent in some exposed strains, lasting even after several cultures in agrochemical-free media, and temporary in others, then returning to the original susceptibility when the contact with the fungicide ceased [ 31 , 169 ]. Other studies using a similar methodology and the same strains also demonstrated that exposure to the fungicide benomyl (mitotic inhibitor) and the herbicides flumioxazin (inhibits protoporphyrinogen oxidase, an enzyme that is important for the synthesis of chlorophyll), isoxaflutole (inhibits the 4-hydroxyphenyl pyruvate dioxygenase), and pendimethalin (inhibits root and shoot growth by preventing plant cell division and elongation) reduced the susceptibility to agrochemicals and clinical antifungals ( https://www.epa.gov/caddis-vol2/caddis-volume-2-sources-stressors-responses-herbicides ) [ 170 , 171 ].…”

Section: Cryptococcus Sppmentioning

confidence: 99%

“…Cross-resistance to fluconazole was also verified in an in vivo murine model for cryptococcosis. The drug proved ineffective in controlling the infection caused by cells previously adapted to tebuconazole, pyraclostrobin, and benomyl, compared to cells nonexposed to fungicides [ 31 , 169 , 171 ].…”

Section: Cryptococcus Sppmentioning

confidence: 99%

“…The molecular mechanism behind cross-resistance selected by environmental azoles, strobilurins, and benzimidazoles, however, has not been fully uncovered. Nonetheless, it seems that fungicide exposure selects mutations in some strains whose resistance strengthens permanently [ 31 , 169 , 171 ]. It is still unclear the role of mutations in these phenotypes.…”

Section: Cryptococcus Sppmentioning

confidence: 99%

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Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

et al. 2021

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Fungal infections are underestimated threats that affect over 1 billion people, and Candida spp., Cryptococcus spp., and Aspergillus spp. are the 3 most fatal fungi. The treatment of these infections is performed with a limited arsenal of antifungal drugs, and the class of the azoles is the most used. Although these drugs present low toxicity for the host, there is an emergence of therapeutic failure due to azole resistance. Drug resistance normally develops in patients undergoing azole long-term therapy, when the fungus in contact with the drug can adapt and survive. Conversely, several reports have been showing that resistant isolates are also recovered from patients with no prior history of azole therapy, suggesting that other routes might be driving antifungal resistance. Intriguingly, antifungal resistance also happens in the environment since resistant strains have been isolated from plant materials, soil, decomposing matter, and compost, where important human fungal pathogens live. As the resistant fungi can be isolated from the environment, in places where agrochemicals are extensively used in agriculture and wood industry, the hypothesis that fungicides could be driving and selecting resistance mechanism in nature, before the contact of the fungus with the host, has gained more attention. The effects of fungicide exposure on fungal resistance have been extensively studied in Aspergillus fumigatus and less investigated in other human fungal pathogens. Here, we discuss not only classic and recent studies showing that environmental azole exposure selects cross-resistance to medical azoles in A. fumigatus, but also how this phenomenon affects Candida and Cryptococcus, other 2 important human fungal pathogens found in the environment. We also examine data showing that fungicide exposure can select relevant changes in the morphophysiology and virulence of those pathogens, suggesting that its effect goes beyond the cross-resistance.

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Section: Cryptococcus Sppmentioning

confidence: 99%

Section: Cryptococcus Sppmentioning

confidence: 99%

Section: Cryptococcus Sppmentioning

confidence: 99%

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Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

et al. 2021

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“…Fungi treated with AITC probably modify the composition of cellular membranes by increasing the level of sterols compared to control samples and I3C treatments and decreasing triacylglycerols to increase their stability. Similarly, the ergosterol synthesis pathway and, specifically, gene erg11 is a target of azole and non-azole fungicides in different fungal species ( 10 , 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Sclerotinia sclerotiorum Response to Long Exposure to Glucosinolate Hydrolysis Products by Transcriptomic Approach

et al. 2021

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Brassica species, including important vegetable crops, such as cabbage, cauliflower, or broccoli, or oil crops, such as rapeseed, produce specific chemical compounds useful to protect them against pests and pathogens. One of the most destructive Brassica diseases in temperate areas around the world is sclerotinia stem rot, caused by the fungus Sclerotinia sclerotiorum .

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“…Fungus treated with AITC probably modify the composition of cellular membranes by increasing the level of sterols in comparison with control and I3C treatments and decreasing tryacylglycerols in order to increase their stability. Similarly, ergosterol synthesis pathway and specifically, gene erg11 are a target of azol and non-azol fungicides in different fungal species (Sellam et al, 2007, Somani et al, 2019, Bastos et al, 2019.…”

Section: Itcs Alter Metabolism Of Proteins and Lipidsmentioning

confidence: 99%

Response of Sclerotinia Sclerotiorum to Long Exposure of Isothiocyanates by Transcriptomics Approach

Madloo

Lema

Cartea

et al. 2021

Preprint

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White mold disease, caused by the necrotrophic fungus Sclerotinia sclerotiorum affects Brassica crops. Brassica crops produce a broad array of compounds such as glucosinolates that contribute to defense against pathogens. From their hydrolysis arise several products with antimicrobial activity called isothiocyanates (ITCs) which toxicity is structure-dependent. It is recognized that S. sclerotiorum is able to overcome the toxic effect of moderate concentrations of ITCs after a prolonged exposure to their action. Our objective was to identify the molecular mechanism underlying response of S. sclerotiorum to long exposure of two chemically diverse ITCs: the aliphatic allyl-ITC (AITC) and the indolic indol-3-carbinol (I3C). We found, with a transcriptomic approach, that the response is dependent of the type of ITC and to their initial target, involving cell membranes in the case of AITC or DNA in the case of I3C. Mechanisms of response include the reorganization of chromatin, mediated by histones chaperones hip4 and cia1, synthesis of ribosomes controlled by the pair kinase-phosphatase aps1-ppn1, catabolism of proteins, synthesis of ergosterol and induction of efflux-pumpers and glutathione transferases. These mechanisms probably help S. sclerotiorum to grow and survive in an environment where ITCs are constantly produced by Brassica plants upon breakdown of glucosinolates.

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From the environment to the host: How non-azole agrochemical exposure affects the antifungal susceptibility and virulence of Cryptococcus gattii

Cited by 22 publications

References 40 publications

Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond

Sclerotinia sclerotiorum Response to Long Exposure to Glucosinolate Hydrolysis Products by Transcriptomic Approach

Response of Sclerotinia Sclerotiorum to Long Exposure of Isothiocyanates by Transcriptomics Approach

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