Azoles are effective antifungal agents used in both medicine and agriculture. They typically work by inhibiting cytochrome P450 enzymes, primarily CYP51 of the ergosterol biosynthesis pathway, thus damaging the fungal cell membrane. However, apart from their desired antifungal properties, several azoles also exhibit endocrine disrupting properties in mammals, both in vitro and in vivo. Here, we have tested two currently used agricultural azole fungicides, triticonazole and flusilazole, for their in vitro anti-androgenic activity and potential effects on reproductive parameters. Both fungicides showed strong androgen receptor (AR) antagonism and disruption of steroid biosynthesis in vitro. Following gestational exposure to flusilazole (15 or 45 mg/kg bw/day) or triticonazole (150 or 450 mg/kg bw/day) in time-mated Sprague Dawley rats, triticonazole induced shorter male anogenital distance (AGD). Flusilazole exposure did not affect the AGD, but altered fetal male blood hormone profile, with increased androstenedione and decreased estrone levels. Flusilazole and triticonazole have dissimilar effects on reproductive parameters in vivo, but both show endocrine disrupting activities.

A risk assessment for freshwater and marine ecosystems is presented for 48 pharmaceutical compounds, belonging to 16 therapeutic classes, and prescribed in northwestern France. Ecotoxicity data were obtained on two freshwater organisms, i.e., crustacean Daphnia magna and the green algae Pseudokirchneriella subcapitata, and on two marine organisms, i.e., the crustacean Artemia salina and the diatom Skeletonema marinoi. Measured environmental concentrations (MEC), in the Orne River and sea off Merville-Franceville in the Basse-Normandie region, were compared to the predicted environmental concentrations (PEC). Predicted no-effect concentrations (PNEC) were derived from acute data for each compound. Then, a risk assessment for each compound and the mixture was performed by calculating risk quotients (RQ as PEC or MEC/PNEC ratio). Results showed that no immediate acute toxicities were expected even if some compounds displayed strong toxicities at very low concentrations. Antibiotics, antidepressants, and antifungals would deserve attention because of their high or median ecological risk suspected on marine and freshwater ecosystems. Marine ecosystems would be more sensitive to pharmaceutical residues.

Attenuating the Taxol biosynthesis by fungi with storage and subculturing is the major challenge that limits their further industrial applications. Aspergillus flavipes has been reported as a potent Taxol producer, with plausible increasing to its Taxol yield upon coculturing with the microbiome of Podocarpus gracilior (El-Sayed et al., Process Biochemistry 76:55–67, 2019a; Scientific Reports 9, 2019b; Enzyme and Microbial Technology 131, 2019c); however, the identity of these microbial inducers remains ambiguous. Thus, this study was to assess the potency of individual microbes to trigger the Taxol biosynthesis by A. flavipes and to unravel the differentially expressed protein in response to bacterial interaction. Among the 25 bacterial endophytes of P. gracilior, Bacillus subtilis was the potent isolate enhancing the Taxol yield of A. flavipes by ~1.6-fold. Strikingly, this bacterial elicitor displayed a reliable inhibition to the growth of A. flavipes, so the released antifungal compound by B. subtilis could be the same signals for triggering the expression of A. flavipes Taxol synthesis. The highest Taxol yield by A. flavipes was obtained with the viable cells of B. subtilis, ensuring the pivotality of physical intimate bacterial-fungal interaction. Differential proteome of the cocultures A. flavipes and B. subtilis as well as the axenic A. flavipes was conducted by LC-MS/MS. From the total of 106 identified proteins, 50 proteins were significantly expressed, 47 were upregulated ones, and 59 were downregulated ones for the cocultures normalizing to the axenic one. From the Gene Ontology (GO) and KEGG enrichment analyses, the cellular process, primary metabolic process, and nitrogen compound metabolic process were significantly changed in the coculture normalizing to monoculture of A. flavipes. The molecular function terms (histones H2B, H2A, peptidyl-prolyl cis-trans isomerase, and nucleoside-diphosphate kinase (NDPK)) were the highly significantly expressed proteins of A. flavipes in response to B. subtilis, with strong correlation to triggering of Taxol biosynthesis. The intimate interaction of A. flavipes with B. subtilis strongly modulates the Taxol biosynthetic machinery of A. flavipes by modulating the chromatin remodeling.

Producing quality food in sufficient quantity while using less agrochemical inputs will be one of the great challenges of the twenty-first century. One way of achieving this goal is to greatly reduce the doses of plant protection compounds by improving the targeting of pests to eradicate. Therefore, we developed a vectorization strategy to confer phloem mobility to fenpiclonil, a contact fungicide from the phenylpyrrole family used as a model molecule. It consists in coupling the antifungal compound to an amino acid or a sugar, so that the resulting conjugates are handled by active nutrient transport systems. The method of click chemistry was used to synthesize three conjugates combining fenpiclonil to glucose or glutamic acid with a spacer containing a triazole ring. Systemicity tests with the Ricinus model have shown that the amino acid promoiety was clearly more favorable to phloem mobility than that of glucose. In addition, the transport of the amino acid conjugate is carrier mediated since the derivative of the L series was about five times more concentrated in the phloem sap than its counterpart of the D series. The systemicity of the L-derivative is pH dependent and almost completely inhibited by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). These data suggest that the phloem transport of the L-derivative is governed by a stereospecific amino acid carrier system energized by the proton motive force.

Pharmaceuticals and personal care products (PPCPs) in the sea area surrounding a densely populated tourist city in southeastern China were investigated. In total, 32 PPCP pollutants classified into 23 categories were detected. Different spatial distribution patterns of PPCPs indicated possible contamination from runoff and multiple local sources. The labile-to-conservative ratios of PPCPs showed the influence of untreated domestic sewage. In addition, increased concentrations of ciprofloxacin, enrofloxacin, and erythromycin around aquaculture farms imply that aquaculture cannot be neglected as a source. The concentrations of oxytetracycline, ranitidine, ciprofloxacin, miconazole, and sulfamethizole were higher in the wet season than those in the dry season, and the difference in pharmaceutical consumption was suspected to be the main driving factor of this seasonal variation. The risk quotients calculated with the maximum concentrations of miconazole, triclosan, dehydronifedipine, and triclocarban exceeded 0.1, indicating potential moderate or high risks. Antibacterial agents in daily chemicals and azole broad-spectrum antifungals were associated with the highest risks in this study; this might be another significant pollution characteristic in the sea area around this subtropical tourist city.

Triclosan (TCS) is an antibacterial and antifungal agent widely used in personal care products, and it has been frequently detected in the aquatic environment. In the present study, the acute toxicity of TCS to Daphnia magna, Photobacterium phosphoreum, Danio rerio, and Limnodrilus hoffmeisteri was assessed under different pH conditions. Generally, TCS was more toxic to the four aquatic organisms in acidic medium. The LC₅₀ values for D. magna and D. rerio were smaller among the selected species, suggesting that D. magna and D. rerio were more sensitive to TCS. In addition, the oxidative stress-inducing potential of TCS was evaluated in Carassius auratus at three pH values. Changes of superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) level, and malondialdehyde (MDA) content were commonly observed in all TCS exposure groups, indicating the occurrence of oxidative stress in the liver of C. auratus. The integrated biomarker response (IBR) index revealed that a high concentration of TCS induced great oxidative stress in goldfish under acidic condition. This work supplements the presently available data on the toxicity data of TCS, which would provide some useful information for the environmental risk assessment of this compound.

In view of the suspected negative impact of synthetic fungicides to the human health, nutritional quality, and non-targeted organisms, the use of plant-based antifungal agents has gained considerable interest to the agri-food industries. The aim of this study was to explore the antifungal and aflatoxin B₁ (AFB₁) inhibitory activity of chitosan (low molecular weight) encapsulated methyl salicylate. The nanoencapsulation of methyl salicylate (Ne-MS) has been characterized by SEM, FTIR, and XRD analysis. The encapsulation efficiency and loading capacity of Ne-MS ranged between 32–34% and 5–7% respectively. The minimum inhibitory concentration of Ne-MS (1.00 μL/mL) against the growth and aflatoxin B₁ production by Aspergillus flavus was found to be lower than the free MS (1.50 μL/mL). Mode of action studies demonstrated that the Ne-MS cause a significant decrease in the ergosterol content, leakage of vital ions (Ca²⁺, Mg²⁺, and K⁺), utilization of different carbon source by the A. flavus. Further, the docking result showed ver1 and omt A gene of AFB₁ biosynthesis are the possible molecular site of action of methyl salicylate. The in situ study revealed that Ne-MS had no significant negative impact on the organoleptic properties of the food system (maize) which strengthen its potential as a biorational alternative of synthetic fungicides.

This study reports the potential of a soil bacterium, Bacillus subtilis strain SPB1, to produce lipopeptide biosurfactants. Firstly, the crude lipopeptide mixture was tested for its inhibitory activity against phytopathogenic fungi. A minimal inhibitory concentration (MIC), an inhibitory concentration at 50 % (IC50 %), and an inhibitory concentration at 90 % (IC90 %) values were determined to be 0.04, 0.012, and 0.02 mg/ml, respectively, for Rhizoctonia bataticola with a fungistatic mode of action. For Rhizoctonia solani, a MIC, an IC50 %, and IC90 % values were determined to be 4, 0.25, and 3.3 mg/ml, respectively, with a fungicidal mode of action. For both of the fungi, a loss of sclerotial integrity, granulation and fragmentation of hyphal mycelia, followed by hyphal shriveling and cell lysis were observed with the treatment with SPB1 biosurfactant fraction. After extraction, separation, and purification, different lipopeptide compounds were identified in the culture filtrate of strain SPB1. Mass spectroscopic analysis confirmed the presence of different lipopeptide compounds consisting of surfactin isoforms with molecular weights of 1007, 1021, and 1035 Da; iturin isoforms with molecular weights of 1028, 1042, and 1056 Da; and fengycin isoforms with molecular weights of 1432 and 1446 Da. Two new clusters of lipopeptide isoforms with molecular weights of 1410 and 1424 Da and 973 and 987 Da, respectively, were also detected. This study reported the ability of a B. subtilis strain to co-produce lipopeptide isoforms with potential use as antifungal compounds.