Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

Abstract

The effects of triazole fungicide Tango® (epoxiconazole) and two neonicotinoid insecticide formulations Mospilan® (acetamiprid) and Calypso® (thiacloprid) were investigated in Candida albicans and three non-albicans species Candida pulcherrima, Candida glabrata and Candida tropicalis to assess the range of morphological, metabolic and genetic changes after their exposure to pesticides. Moreover, the bioavailability of pesticides, which gives us information about their metabolization was assessed using gas chromatography-mass spectrophotometry (GC-MS). The tested pesticides caused differences between the cells of the same species in the studied populations in response to ROS accumulation, the level of DNA damage, changes in fatty acids (FAs) and phospholipid profiles, change in the percentage of unsaturated to saturated FAs or the ability to biofilm. In addition, for the first time, the effect of tested neonicotinoid insecticides on the change of metabolic profile of colony cells during aging was demonstrated. Our data suggest that widely used pesticides, including insecticides, may increase cellular diversity in the Candida species population-known as clonal heterogeneity-and thus play an important role in acquiring resistance to antifungal agents.

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

“…albicans was not able to form hyphae ( Fig 2B ). Tango Star, which inhibits ergosterol synthesis, may contribute to depleting the intracellular pool of ergosterol while blocking the transition of blastospores during hyphae formation [ 145 ]. The overall response to agrochemical stress in C .…”

“…glabrata and to a lesser extent in C . tropicalis was the selection of subpopulations with increased fatty acid unsaturation rates [ 145 ]. Treatments with Tango Star also aggravated the total DNA damage in C .…”

Collateral consequences of agricultural fungicides on pathogenic yeasts: A One Health perspective to tackle azole resistance

“…Cross‐resistance to medical and agricultural azoles has also been found in clinically relevant Candida and other yeasts from cultivated areas, raising the hypothesis that azole fungicides may also trigger cross‐resistance in yeasts 24 . Indeed, in vitro studies have associated exposure to azoles fungicides with decreasing susceptibility to medical azoles in various Candida and/or Cryptococcus species 25‐31 . As an example, in vitro exposure to prochloraz leads to stable fluconazole and voriconazole resistance in C glabrata 25 .…”

“…Similarly, exposure to tebuconazole and tetraconazole selects for resistance to fluconazole in C parapsilosis , C orthopsilosis and C metapsilosis 29 . Besides antifungal resistance, some studies underlined other genotypic/phenotypic changes, such as genetic instability 31 or increased virulence 32 . Some experiments identified active efflux and/or overexpression of the gene encoding the azole target lanosterol 14‐alpha‐demethylase as possible mechanisms explaining cross‐resistance with medical azoles 25‐27,29 .…”

“…Some in vitro studies support fungicide exposure, especially to agricultural azoles, as a contributor to this phenomenon. However, azoles are probably not the only agrochemical compounds capable of selecting resistance to medical azoles, as in vitro exposure to strobilurins, natamycin, benomyl and non‐fungicide compounds, have been shown to affect the in vitro susceptibility to azole antifungals or polyenes, possibly due to non‐target‐site resistance mechanisms such as efflux 28,30,31,96 …”