Design, Synthesis, and Antifungal Activities of Phenylpyrrole Analogues Based on Alkaloid Lycogalic Acid.

Plant diseases caused by pathogenic fungi seriously affect the yield and quality of crops, cause huge economic losses, and pose a considerable threat to global food security. Phenylpyrrole analogues were designed and synthesized based on alkaloid lycogalic acid. All target compounds were characterized by 1H NMR, 13C NMR, and HRMS. Their antifungal activities against seven kinds of phytopathogenic fungi were evaluated. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 µg/mL; 14 compounds displayed more than 60% fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum, and in particular, the fungicidal activities of compounds 8g and 8h against Rhizoctonia cerealis were more than 90%, which could be further developed as lead agents for water-soluble fungicides. The molecular docking results indicate that compounds 8g and 8h can interact with 14α-demethylase (RcCYP51) through hydrogen bonding with strong affinity.

Bioactivities evaluation of an endophytic bacterial strain Bacillus tequilensis QNF2 inhibiting apple ring rot caused by Botryosphaeria dothidea on postharvest apple fruits.

Apple ring rot, one of the most common apple postharvest diseases during storage, is caused by Botryosphaeria dothidea. Presently, the disease management is primarily dependent on chemical fungicide application. Here we demonstrated an endophyte bacterium Bacillus tequilensis QNF2, isolated from Chinese leek (Allium tuberosum) roots considerably suppressed B. dothidea mycelial growth, with the highest suppression of 73.56 % and 99.5 % in the PDA and PDB medium, respectively in vitro confront experiments. In in vivo experiments, B. tequilensis QNF2 exhibited a control efficacy of 88.52 % and 100 % on ring rot disease on postharvest apple fruits inoculated with B. dothidea disc and dipped into B. dothidea culture, respectively. In addition, B. tequilensis QNF2 volatile organic compounds (VOCs) also manifested markedly inhibition against B. dothidea mycelial growth and the ring rot on postharvest apple fruits. Moreover, B. tequilensis QNF2 severely damaged the mycelial morphology of B. dothidea. Finally, B. tequilensis QNF2 significantly repressed the expression of six pathogenicity-related genes, such as adh, aldh, aldh3, galm, pdc1, pdc2, involved in glycolysis/gluconeogenesis of B. dothidea. The findings of the study proved that B. tequilensis QNF2 was a promising alternative for controlling apple ring rot of postharvest apple fruit.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Deciphering the mechanisms involved in reduced sensitivity to azoles and fengycin lipopeptide in Venturia inaequalis.

Apple scab, caused by the hemibiotrophic fungus Venturia inaequalis, is currently the most common and damaging disease in apple orchards. Two strains of V. inaequalis (S755 and Rs552) with different sensitivities to azole fungicides and the bacterial metabolite fengycin were compared to determine the mechanisms responsible for these differences. Antifungal activity tests showed that Rs552 had reduced sensitivity to tebuconazole and tetraconazole, as well as to fengycin alone or in a binary mixture with other lipopeptides (iturin A, pumilacidin, lichenysin). S755 was highly sensitive to fengycin, whose activity was close to that of tebuconazole. Unlike fengycin, lipopeptides from the iturin family (mycosubtilin, iturin A) had similar activity on both strains, while those from the surfactin family (lichenysin, pumilacidin) were not active, except in binary mixtures with fengycin. The activity of lipopeptides varies according to their family and structure. Analyses to determine the difference in sensitivity to azoles (which target the CYP51 enzyme involved in the ergosterol biosynthesis pathway) showed that the reduced sensitivity in Rs552 is linked to (i) a constitutive increased expression of the Cyp51A gene caused by insertions in the upstream region and (ii) greater efflux by membrane pumps with the involvement of ABC transporters. Microscopic observations revealed that fengycin, known to interact with plasma membranes, induced morphological and cytological changes in cells from both strains. Sterol and phospholipid analyses showed a higher level of ergosta-7,22-dien-3-ol and a lower level of PI(C16:0/C18:1) in Rs552 compared with S755. These differences could therefore influence the composition of the plasma membrane and explain the differential sensitivity of the strains to fengycin. However, the similar antifungal activities of mycosubtilin and iturin A in the two strains indirectly indicate that sterols are probably not involved in the fengycin resistance mechanism. This leads to the conclusion that different mechanisms are responsible for the difference in susceptibility to azoles or fengycin in the strains studied.

Effectiveness of Fludioxonil, a New-Generation Reduced-Risk Fungicide, Against Brown Rot Pathogens.

Brown rot, caused by Monilinia species, is a destructive disease of pome and stone fruits that can lead to significant losses in production. Disease management is mainly based on fungicide applications during the growing season. Fludioxonil, a "new-generation reduced-risk fungicide", is one of the most important fungicide used. The objectives of the present study were to compare and determine the toxicity of fludioxonil to selected M. laxa, M. fructigena and M. fructicola isolates, to test its effectiveness in detached fruits and to assess its effectiveness under practical control conditions. A total of 27 isolates (10 isolates of M. laxa, 8 of M. fructigena and 9 of M. fructicola) were tested for sensitivity to fludioxonil in vitro. Isolates from each species exhibited a homogeneous response to the fungicide, while differences among the different species were determined. Based on calculated resistance factors (RF), the examined isolates were classified into two categories: sensitive and moderately resistant. In vivo testing of the effectiveness of the label concentration of fludioxonil on detached fruit did not reveal differences between isolates classified into different sensitivity categories; fludioxonil used at the label concentration (0.1%) inhibited decay development 93.5 to 100%, regardless of the isolate category. Field trials revealed the very high efficacy of fludioxonil in preventing brown rot on fruits, ranging from 92.2 to 100 for peach, 90.7 to 97.3 for plum and 84.9 to 91.9% for sour cherry. In conclusion, fludioxonil was highly effective according to in vitro sensitivity tests and when used under practical field conditions for brown rot control.

Risk assessment of resistance to prochloraz in Phoma arachidicola causing peanut web blotch.

Peanut web blotch (PWB) caused by Phoma arachidicola, is one of the most serious foliar diseases of peanut. Although prochloraz is an active fungicide with broad anti-fungal spectrum, it has not been registered for the control of PWB in China. The activity of prochloraz against P. arachidicola and the risk of resistance to prochloraz in P. arachidicola are still unclear. In current study, the inhibitory activity of prochloraz against 96 P. arachidicola strains was determined with the average EC50 value of 1.2700 ± 0.7786 µg/mL. Prochloraz exhibited excellent protective and curative effect on detached peanut leaves, and the effect was obviously better than that of carbendazim and difenoconazole at the same concentration. After prochloraz treatment, the mycelium of P. arachidicola contorted, shrunk and ruptured, with shrinking of cell wall and membrane, enhanced cell membrane permeability, and reduced ergosterol content. Totally 80 prochloraz-resistant mutants were obtained by fungicide adaptation with the frequency of 6.7 × 10-3. All the selected 12 prochloraz-resistant mutants lost their resistance to prochloraz after 10 transfers on PDA plates. And these mutants exhibited decreased biological fitness in mycelial growth and pathogenicity. Moreover, there was positive cross-resistance between prochloraz and other demethylation inhibitor (DMI) fungicides, such as tebuconazole, triflumizole and difenoconazole, but no cross-resistance was found between prochloraz and other classes of fungicides, such as carbendazim, pydiflumetofen or fludioxonil. Overexpression of PaCYP51 and PaAtrB genes were detected in the resistant mutants. All the above results demonstrated that prochloraz has a great potential in management of PWB. The risk of P. arachidicola developing resistance to prochloraz is relatively low-to-medium. Overexpressing of PaCYP51 and PaAtrB might be linked to prochloraz resistance in P. arachidicola.

Identification of plant based potential antifungal compounds against BMK-1 protein of Bipolaris oryzae using molecular docking approach.

Rice brown spot is an important disease of rice worldwide that inflicts substantial yield losses. The antimicrobial potential of methanol, acetone and dimethyl sulfoxide (DMSO) extracts of different medicinal plants, viz., Syzygium aromaticum, Saussurea costus, Acorus calamus, Bergenia ciliate, Geranium pratense, Mentha longifolia, Inula racemosa, Podophyllum hexandrum, Heracleum candicans and Picrorhiza kurroa, against the brown spot pathogen Bipolaris oryzae in vitro was evaluated via mycelial growth inhibition and spore germination inhibition assays. Among the plant extracts tested, 100% mycelial inhibition was observed for the methanol extract of Syzygium aromaticum at all three concentrations (2000 ppm, 3000 ppm and 4000 ppm), followed by the methanol extract of Inula racemosa (90.33%) at 4000 ppm. A maximum conidial germination inhibition of 83.54% was exhibited by the Heracleum candicans leaf extract. Phytochemical profiling of Syzygium aromaticum and Inula racemosa through liquid chromatography and mass spectrometry (HR-LCMS) revealed the presence of several compounds, such as eugenol, ursolic acid, quercetin, chlorogenic acid, and noscapine. A molecular docking approach was used to identify key inhibitory molecules against B. oryzae. Among the compounds detected in S. aromaticum and Inula racemosa, ursolic acid and noscapine were found to have the greatest binding affinity for the Big Mitogen Activated Protein Kinase (BMK-1) enzyme present in B. oryzae. In conclusion, S. aromaticum and Inula racemosa are potent compounds that could serve as lead compounds for drug discovery in the future.

Pseudomonas protegens volatile organic compounds inhibited brown rot of postharvest peach fruit by repressing the pathogenesis-related genes in Monilinia fructicola.

Brown rot, caused by Monilinia fructicola, is considered one of the devasting diseases of pre-harvest and post-harvest peach fruits, restricting the yield and quality of peach fruits and causing great economic losses to the peach industry every year. Presently, the management of the disease relies heavily on chemical control. In the study, we demonstrated that the volatile organic compounds (VOCs) of endophyte bacterial Pseudomonas protegens QNF1 inhibited the mycelial growth of M. fructicola by 95.35% compared to the control, thereby reducing the brown rot on postharvest fruits by 98.76%. Additionally, QNF1 VOCs severely damaged the mycelia of M. fructicola. RNA-seq analysis revealed that QNF1 VOCs significantly repressed the expressions of most of the genes related to pathogenesis (GO:0009405) and integral component of plasma membrane (GO:0005887), and further analysis revealed that QNF1 VOCs significantly altered the expressions of the genes involved in various metabolism pathways including Amino acid metabolism, Carbohydrate metabolism, and Lipid metabolism. The findings of the study indicated that QNF1 VOCs displayed substantial control efficacy by disrupting the mycelial morphology of M. fructicola, weakening its pathogenesis, and causing its metabolic disorders. The study provided a potential way and theoretical support for the management of the brown rot of peach fruits.

Carrier-free self-assembled nanoparticles based on prochloraz and fenhexamid for reducing toxicity to aquatic organism.

Nanoformulations of pesticides are an effective way to increase utilization efficiency and alleviate the adverse impacts on the environments caused by conventional pesticide formulations. However, the complex preparation process, high cost, and potential environmental risk of nanocarriers severely restricted practical applications of carrier-based pesticide nanoformulations in agriculture. Herein, carrier-free self-assembled nanoparticles (FHA-PRO NPs) based on fenhexamid (FHA) and prochloraz (PRO) were developed by a facile co-assembly strategy to improve utilization efficiency and reduce toxicity to aquatic organism of pesticides. The results showed that noncovalent interactions between negatively charged FHA and positively charged PRO led to core-shell structured nanoparticles arranged in an orderly manner dispersing in aqueous solution with a diameter of 256 nm. The prepared FHA-PRO NPs showed a typical pH-responsive release profile and exhibited excellent physicochemical properties including low surface tension and high max retention. The photostability of FHA-PRO NPs was improved 2.4 times compared with free PRO. The FHA-PRO NPs displayed superior fungicidal activity against Sclerotinia sclerotiorum and Botrytis cinerea and longer duration against Sclerotinia sclerotiorum on potted rapeseed plants. Additionally, the FHA-PRO NPs reduced the acute toxicity of PRO to zebrafish significantly. Therefore, this work provided a promising strategy to develop nanoformulations of pesticides with stimuli-responsive controlled release characteristics for precise pesticide delivery.

De novo assembly and characterization of the transcriptome of Morchella esculenta growth with selenium supplementation.

Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta. While 5 µg mL-1selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL-1significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL-1 and 10 µg mL-1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.

Antifeedant, antifungal and nematicidal compounds from the endophyte Stemphylium solani isolated from wormwood.

The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, from the medicinal plant Artemisia absinthium, along with the antifungal, insect antifeedant and nematicidal compounds present in the extract. The endophyte Aa22 was identified as Stemphylium solani by molecular analysis. The antifungal activity was tested by broth microdilution against Fusarium solani, F. oxysporum, F. moniliforme and Botrytis cinerea, the insect antifeedant by choice bioassays against Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi and the in vitro mortality against the root-knot nematode Meloiydogyne javanica. The structures of bioactive compounds were determined on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The ethyl acetate extract obtained from the solid rice fermentation showed mycelial growth inhibition of fungal pathogens (EC50 0.08-0.31 mg/mL), was antifeedant to M. persicae (99%) and nematicidal (68% mortality). A bioguided fractionation led to the isolation of the new compound stempholone A (1), and the known stempholone B (2) and stemphol (3). These compounds exhibited antifeedant (EC50 0.50 mg/mL), antifungal (EC50 0.02-0.43 mg/L) and nematicidal (MLD 0.5 mg/mL) activities. The extract activities can be explained by 3 (antifungal), 1-3 (antifeedant) and 1 (nematicidal). Phytotoxicity tests on Lolium perenne and Lactuca sativa showed that the extract and 1 increased L. sativa root growth (121-130%) and 1 reduced L. perenne growth (48-49%). These results highlight the potential of the endophytic fungi Aa22 as biotechnological source of natural product-based biopesticides.

Escuzarmycins A-D, Potent Biofungicides to Control Septoria tritici Blotch.

A study targeting novel antifungal metabolites identified potent in vitro antifungal activity against key plant pathogens in acetone extracts of Streptomyces sp. strain CA-296093. Feature-based molecular networking revealed the presence in this extract of antimycin-related compounds, leading to the isolation of four new compounds: escuzarmycins A-D (1-4). Extensive structural elucidation, employing 1D and 2D NMR, high-resolution mass spectrometry, Marfey's analysis, and NOESY correlations, confirmed their structures. The bioactivity of these compounds was tested against six fungal phytopathogens, and compounds 3 and 4 demonstrated strong efficacy, particularly against Zymoseptoria tritici, with compound 3 exhibiting the highest potency (EC50: 11 nM). Both compounds also displayed significant antifungal activity against Botrytis cinerea and Colletotrichum acutatum, with compound 4 proving to be the most potent. Despite moderate cytotoxicity against the human cancer cell line HepG2, compounds 3 and 4 emerge as promising fungicides for combating Septoria tritici blotch, anthracnose, and gray mold.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3), and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Antifungal effects of volatile organic compounds produced by Trichoderma hamatum against Neocosmospora solani.

Neocosmospora solani causes Fusarium wilt disease and root rot, which are serious problems worldwide. To determine the growth inhibition of Neocosmospora solani by Trichoderma hamatum volatile organic compounds (VOCs), the major chemical components of Trichoderma hamatum VOCs and the differences in their contents at different times were analysed, and the activity of these components was evaluated. The antifungal activity of Trichoderma hamatum was measured by a screening test, as Trichoderma hamatum exhibited strong antagonism against Neocosmospora solani in vitro. The double plate technique was used to verify the activity of Trichoderma hamatum VOCs, and the inhibition rate was 63.77%. Neocosmospora solani mycelia were uneven and expanded, the contents of the cells leaked, and the mycelia shrank and presented a diaphragm in the hyphae upon Trichoderma hamatum VOCs treatment. Trichoderma hamatum VOCs and their contents at different times were analysed by using gas chromatography-mass spectrometry. 6-Pentyl-2H-pyran-2-one clearly presented in greater amounts than the other components on day 3, 4, 5, and 6. VOCs from Trichoderma hamatum exhibited evident effects on the percentage of healthy fruit after day 3. Moreover, Trichoderma hamatum can improve the biological control of diseases caused by soilborne pathogens, and can be applied in biocontrol fields.

Design, Synthesis, and Antifungal Activities of Novel Potent Fluoroalkenyl Succinate Dehydrogenase Inhibitors.

The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness of fungicides in agricultural production. In this study, a series of novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated for their antifungal activities against eight fungi. The results from the in vitro antifungal assay demonstrated that compound 34 exhibited superior activity against Rhizoctonia solani with an EC50 value of 0.04 µM, outperforming commercial fluxapyroxad (EC50 = 0.18 µM) and boscalid (EC50 = 3.07 µM). Furthermore, compound 34 showed similar effects to fluxapyroxad on other pathogenic fungi such as Sclerotinia sclerotiorum (EC50 = 1.13 µM), Monilinia fructicola (EC50 = 1.61 µM), Botrytis cinerea (EC50 = 1.21 µM), and also demonstrated protective and curative efficacies in vivo on rapeseed leaves and tomato fruits. Enzyme activity experiments and protein-ligand interaction analysis by surface plasmon resonance revealed that compound 34 had a stronger inhibitory effect on succinate dehydrogenase compared to fluxapyroxad. Additionally, molecular docking and DFT calculation confirmed that the fluoroalkenyl unit in compound 34 could enhance its binding capacity with the target protein through p-π conjugation and hydrogen bond interactions.

Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature.

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.

Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.

Design, Synthesis, and Antifungal Evaluation of Diverse Heterocyclic Hydrazide Derivatives as Potential Succinate Dehydrogenase Inhibitors.

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 µg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 µg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 µg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 µM, respectively, which were superior to that of boscalid (IC50 = 2.38 µM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.

Chemical Composition and Antimicrobial Properties of Morchella crassipes (Ascomycota) from Kashmir Valley (India).

In the current era, wild macrofungi are being focused for developing and overing novel bioactive compounds for the management of agricultural, horticultural, and other infectious diseases. In that view, current research work was designed to evaluate the biochemical composition and medicinal properties of Morchella crassipes mushroom. The mycochemical screening of aqueous extract exposed the incidence of glycosides, free amino acids and proteins, alkaloids, carbs, flavonoids, terpenoids, phenolic compounds and tannins, except volatile oils, resins, steroids, and anthraquinones. However, hexane extract exhibited the occurrence of glycosides, alkaloids, volatile oils, steroids and terpenoids while as all other phytochemicals were not detected. The gas chromatography mass spectrometry profiling has disclosed the identification of three predominant naturally occurring bioactive volatile monoterpenoids, namely neral, citral, and epoxy-linalool oxide with well-known biological activities. The methanolic extract resulted in strong antifungal efficacy against the tested fungal strains such as Penicillium chrysogenum (20.33 ± 0.57 mm) followed by Pythium ultimum (15.33 ± 0.76 mm) and Aspergillus niger (12.50 ± 0.50 mm) at highest concentrations. Likewise, marked antibacterial effects were reported in case of Staphylococcus aureus (15.16 ± 0.76 mm), followed by Salmonella gallinarum (14.33 ± 0.57 mm) and Escherichia coli (13.66 ± 0.57 mm), respectively. This data may offer baseline information regarding the bioactive metabolites and opening new ways for conducting trails to find natural management strategies to combat multi drug resistant pathogens in horticulture, agriculture, and aquaculture.

A comparative study of the biosynthesis of CuNPs by Niallia circulans G9 and Paenibacillus sp. S4c strains: characterization and application as antimicrobial agents.

BACKGROUND: Biosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents. RESULTS: This investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV-visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs' SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13-100 nm by the G9 strain and spherical nanoparticles with a size range of 5-40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883. CONCLUSION: The present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.