Fluorinated isocyanates and their derivatives as intermediates for biologically active compounds.
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From the results of application of various inhibitors, or combinations of inhibitors to cell suspensions of the yeast Torulopsis candida and by determination of O2-consumption and growth rates it is concluded, that a main site of action of tridemorph is localized in the pathway of the respiratory chain. Tridemorph inhibits as well the respiration as the growth of T. candida depending on the concentration and the time of exposition. Tridemorph does not uncouple respiration but inhibits the uncoupled respiration to the same extent. Inhibition of respiration and growth by tridemorph is enhanced by suboptimal concentrations of antimycin A, oligomycin, rotenone, and 2,4-dinitrophenole. That leads to the conclusion that these inhibitors essentially enlarge the permeability for tridemorph which can be more rapidly transported to the site of action.
Two unicellular and two filamentous cyanobacteria (blue-green algae) were exposed under conditions optimal for photoautotrophic growth to eleven pesticides. Low concentrations (0.01 to 5 ppm) of diuron, atrazine, and paraquat inhibited growth. With MCPA, MCPP, 2,4-D, milstem and ethrel, marked inhibitory effects were achieved only at concentrations above 100 ppm. Growth was inhibited by glyphosate, DDT, and thiram at intermediate concentrations. In some cases, the effective concentration of the pesticide varied considerably with the organism tested.
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Chitin synthase from Coprinus cinereus (Schaeff. ex Fr.) S. F. Gray (= C. lagopus sensu Buller) was used as a model for chitin synthase from insects. The effect of dimilin (difluorobenzuron), captan (trichloromethylsulfonyl fungicide), kitazin P (organophosphorus ester fungicide) and parathion (organophosphorus insecticide) on the fungal enzyme was compared with the effect of nikkomycin (nucleosidepeptide antibiotic).
Aspergillus fumigatus was the most frequently isolated thermophilous fungus from green leaf surfaces. The application of fungicides significantly reduced the frequency of its occurrence there. A. fumigatus was relatively tolerant to fungicides. On Captan-, Thiram-, and Verdasan-treated leaves, A. fumigatus constituted 66%--80% of the total number of isolates obtained at 45 degrees C from each treatment while Dicloran did not depress the percentages. At 45 degrees C, A. fumigatus was found to be strongly cellulolytic with a slow rate of radial extension on YpSs agar and rapid rate of mycelial growth in Czapek Dox liquid medium. Increasing concentrations of all four fungicides reduced or prevented growth, sporulation, starch depletion and cellulose clearing of A. fumigatus. The fungus could tolerate higher concentrations of HgCl2 than of Verdasan. 2.5 microgram/ml of the four fungicides altered the rates of mycelial growth but not the maximum amount of mycelial dry weight attained.
A number of diverse compounds including divalent metal ions, simple sugars, and common counterions, buffers, and fungicides were surveyed in the laboratory with regard to ability to inhibit germination of field-collected sclerotia from Whetzelinia sclerotiorum. Many compounds were inhibitory and several were comparable in effectiveness to benomyl and other commercial fungicides. Different levels of a given inhibitor were needed to prevent stipe formation, apothecial formation or mycelial germination. Inhibition was not correlated with ionic strength or related to pH.
The growing burden of fungal diseases on human, animal, plant, and environmental health is a serious global problem that requires a "One Health" approach beyond disciplinary silos. Fungal diseases are often neglected, yet their prevalence and importance are increasing at an alarming rate. Complex interactions among different host organisms, coupled with human activities, anthropogenic environmental impacts, climate change, globalization, and antifungal drug use, particularly in agriculture, are significant contributing factors. The emergence and spread of resistance to existing antifungal agents is one of the most important consequences, leading to poor treatment outcomes in both clinical and agricultural settings. Azole fungicides used in crops have been associated with the selection of resistant strains in some fungi common in the environment and associated with human disease, such as Aspergillus flavus and Fusarium spp., which have a unique enzyme paralogue cyp51C, and efflux pumps that flush out the azoles, thereby leading directly to treatment failure. The article explains how fungal pathogens can affect each of the three pillars of One Health. In plant health, fungal infections affect food security and economic outcomes, while the use of fungicides for treatment can lead to cross-resistance with clinical medications. In animal health, fungal diseases affect livestock well-being and productivity, and animals act as reservoirs for the zoonotic transmission of resistant strains to humans. In human health, the impact on immunocompromised populations is high, as invasive fungal infections result in significant morbidity and mortality. Limited availability of antifungal drugs, diagnostic challenges, and limited surveillance. To combat these multifaceted, interconnected challenges, a collaborative, multisectoral approach is imperative. Looking ahead, future initiatives should emphasize genomic and eco-epidemiological research to elucidate the drivers of emergence, anticipate outbreaks, and identify emerging threats. In conclusion, addressing the global burden of fungal diseases necessitates a holistic One Health approach that aligns surveillance, research, policy, and public health interventions to preserve the efficacy of existing treatments and protect the health of all interconnected domains.
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Mutants resistant to two fungicides, chloroneb (1,4-dichloro-2,5-dimethoxybenzene) and vitavax (2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin) were spontaneously obtained from a strain of Aspergillus nidulans with frequencies of 12.5 and 1.1 respectively, in 10(8) conidia. One chloroneb-resistant mutant (Chl 1) segregated as a single gene and was mapped in linkage group IV. It also caused a partial dependence of the strain on the fungicide and was semi-dominant. The mutant resistant to vitavax (Vit 1) also segregated as a single gene and was dominant. Both fungicides altered the instability of diploid and duplication strains. Chloroneb mainly increased haploidization, and vitavax reduced the mitotic recombination in diploids. Chloroneb increased the instability of duplication strains, and vitavax reduced such instability. The possible mode of action of such fungicides affecting stability is discussed.
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Thiabendazole, 2-(4'-thiazolyl)benzimidazole, at 80 micrometer completely inhibits mitosis in hyphae of Aspergillus nidulans, growing in liquid culture. DNA and RNA synthesis and mycelial growth are only partially inhibited at this concentration. Binding studies with cell-free mycelial extracts from Penicillium expansum showed that thiabendazole competitively inhibits [14C]carbendazim binding to tubulin, which suggests that the antimitotic activity of thiabendazole is based on interference with microtubule assembly. Tubulin from a thiabendazole-resistant and carbendazim-highly sensitive mutant of P. expansum has a lower affinity to thiabendazole and a higher affinity to carbendazim than tubulin from a wide-type strain. This indicates that in this mutant the structure of the binding site is affected. The data presented suggest that several sites of both the tubulin and ligand molecule are involved in the binding of benzimidazole compounds to fungal tubulin.
Tebuconazole, a widely used ergosterol biosynthesis-inhibiting fungicide, can affect nontargets, especially when combined with insecticides. We employed label-free quantitative proteomics to investigate the effects of long-term exposure to sublethal concentrations (100 μg/L) of tebuconazole, either by itself or alongside the neonicotinoid thiacloprid (100 μg/L), on the heads of Bombus terrestris workers. A Bayesian factor power analysis revealed that the experiment produced conclusive proteomic results. Tebuconazole treatment revealed eleven differentially abundant proteins, which increased elevenfold with thiacloprid. The proteins that changed in the same direction in both treatments suggest the occurrence of epigenetic events because they are involved in histone trimethylation (H3K4me3), pre-mRNA processing, and folate (vitamin B9) metabolism. Following co-exposure, the abundance of histone H2A.V and its associated proteins was affected. Two important detoxification-related proteins, CYP6BE1 and CYP6AQ1 (honey bee homologs), were identified, as well as proteins that suggest hormonal and neurotoxic effects. Overall, this study suggests that tebuconazole affects key epigenetic processes in bumblebee heads at the proteome level, though this was not confirmed at the biological level or through orthogonal methods. The tested chemicals were previously found to affect trimethylations, but not H3K4me3. We suggest analyzing the different trimethylations, their interplay, and associated hallmarks, such as folate levels. SIGNIFICANCE: The effects of pesticides and their combinations on organisms can be unexpected until they are examined using modern, complex methods. High-throughput proteomics can provide data on important biochemical processes affected by pesticides, offering a different perspective to that at the expression level. Despite their low acute toxicity, a group of fungicides that inhibit (ergo)sterol biosynthesis (EBI or SBI) are considered dangerous to pollinators, including bumblebees. This is due to the increasing toxicity of insecticides through the inhibition of cytochrome P450 detoxification enzymes. We found that tebuconazole had a similar effect on epigenetic events when used alone or in combination with the insecticide thiacloprid. Key proteins suggest that H3K4 histone trimethylation (H3K4me3) was impacted. To our knowledge, this expands the existing evidence suggesting that tebuconazole/triazole fungicides affect histone trimethylation H3K27me3. Since literature shows that thiacloprid affects H3K9me3, it is possible that thiacloprid and tebuconazole interact in these epigenetic events that affect each other. Overall, our results suggest that tebuconazole affects proteins involved in histone trimethylation, pre-mRNA processing, and folate metabolism. These are all hallmarks of epigenetic processes and were further extended by the co-exposure of tebuconazole and thiacloprid to more differently abundant proteins. Additionally, the results provide data on cytochrome P450s of the CYP6 family, which act as detoxifying proteins, as well as proteins that indicate hormonal and neurotoxic effects in bumblebee heads. Finally, the results of the Bayesian power analysis confirmed the meaningfulness of the proteomic data analyzed in this study. If the new findings obtained at the proteome level are verified by different methods, the full extent of the side effects of tebuconazole can be revealed.
Thifluzamide (TF) is a widely used phenyl urea fungicide in rice production; however, its impacts on the structural composition and functional dynamics of the rhizosphere microbiome remain poorly understood. Here, we systematically investigated the effects of TF on the structure, interactions, and functional potential of the rice (Oryza sativa L.) rhizosphere microbiome using integrated amplicon sequencing and metagenomic approaches. TF application significantly altered both bacterial and fungal community composition, bacterial diversity was markedly reduced, whereas fungal diversity increased. With bacterial diversity markedly reduced while fungal diversity increased. Beta-diversity analyses revealed strong treatment-driven community separation, indicating pronounced TF-induced microbial restructuring. Co-occurrence network analysis demonstrated reduced complexity and connectivity in bacterial networks but increased negative co-occurrence patterns within fungal communities, suggesting contrasting stability responses between microbial kingdoms. Metagenomic profiling further revealed substantial functional shifts, including the differential enrichment of KEGG and COG pathways associated with xenobiotic metabolism. Notably, while total ARG abundance remained stable, TF exposure altered the resistome profile by selectively enriching specific classes of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and mobile genetic elements (MGEs). Strong positive correlations between MGEs and ARGs highlighted an elevated potential for horizontal gene transfer. Metagenome-assembled genome (MAG) analysis identified specific TF-enriched bacterial taxa, including Methylophilus, Sulfurospirillum, and Azospirillum, which harbored genes involved in pesticide degradation and xenobiotic transformation. Collectively, these findings demonstrate that TF profoundly reshapes the rice rhizosphere microbiome by altering microbial diversity, interaction networks, resistance gene profiles, and functional capacities. This study provides genomic insights into fungicide-microbiome interactions, underscoring the potential ecological implications associated with TF application, while identifying candidate microbial taxa that may contribute to pesticide degradation and rhizosphere microecology resilience.
Chiral fungicides constitute a substantial proportion of commonly used pesticides; however, the spread of antibiotic resistance genes (ARGs) in agricultural settings under repeated exposure to different enantiomers is still unclear. Here, the prevalence and potential risks of ARGs were investigated in the soil-earthworm ecosystem when exposed to hexaconazole (HEX) enantiomers. Metagenomic analysis indicated that R-HEX and S-HEX facilitated the dissemination of ARGs in soil without earthworms, but this effect diminished with successive exposures. Notably, S-HEX exhibited a greater effect on ARG profiles compared to R-HEX. Furthermore, HEX enantiomers, particularly S-HEX, increased the mobility potential of ARGs and enhanced host pathogenicity, thereby contributing to elevated ecological risks. Specifically, exposure to the HEX enantiomer led to an enrichment of dominant pathogenic ARG hosts, such as Enterobacteriaceae. Importantly, earthworms alleviated the enantiomer-driven dissemination of ARGs and weakened their association with mobile genetic elements (MGEs). Overall, this study offers novel perspectives on the enantiomer-driven propagation of ARGs induced by the chiral pesticide hexaconazole in soil and highlights the role of earthworms in mitigating ARG contamination. These findings contribute significantly to the risk assessment and remediation strategies for chiral pesticides.
A histoenzymic study of cerebral phosphatases and esterases was performed on rats subjected to experimental intoxication with mercury phenylacetate. Following intragastric application of mercury phenylacetate to experimental animals, decreased activities of cerebral ATPase, acP and AChE were observed. The intoxicated animals displayed enhanced cerebral TPPase and partially also NsChE activities. Apart from changes in the histoenzymic pattern of the experimental brains, the ingestion of mercury phenylacetate brought about evident morphological changes in form of neuronal vacuolisation and spongious degeneration of the white matter. The extent of morphological as well as histoenzymic alterations was dependent on the duration of the experimental poisoning.
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