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

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 use...

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Main Authors: Rafael W Bastos, Luana Rossato, Gustavo H Goldman, Daniel A Santos
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-12-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010073&type=printable
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author Rafael W Bastos
Luana Rossato
Gustavo H Goldman
Daniel A Santos
author_facet Rafael W Bastos
Luana Rossato
Gustavo H Goldman
Daniel A Santos
author_sort Rafael W Bastos
collection DOAJ
description 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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spelling doaj-art-9dba79ed41684c3db769c1011e93abeb2025-08-20T02:02:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-12-011712e101007310.1371/journal.ppat.1010073Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.Rafael W BastosLuana RossatoGustavo H GoldmanDaniel A SantosFungal 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010073&type=printable
spellingShingle Rafael W Bastos
Luana Rossato
Gustavo H Goldman
Daniel A Santos
Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
PLoS Pathogens
title Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
title_full Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
title_fullStr Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
title_full_unstemmed Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
title_short Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.
title_sort fungicide effects on human fungal pathogens cross resistance to medical drugs and beyond
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010073&type=printable
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AT luanarossato fungicideeffectsonhumanfungalpathogenscrossresistancetomedicaldrugsandbeyond
AT gustavohgoldman fungicideeffectsonhumanfungalpathogenscrossresistancetomedicaldrugsandbeyond
AT danielasantos fungicideeffectsonhumanfungalpathogenscrossresistancetomedicaldrugsandbeyond