Abstract Ergosterol,（1→3）-α-D-glucan and chitosan are important biomaterials. In this research, a process has been developed to integratively extract ergosterol, （1→3）-α-D-glucan, and chitosan from Penicillium...Abstract Ergosterol,（1→3）-α-D-glucan and chitosan are important biomaterials. In this research, a process has been developed to integratively extract ergosterol, （1→3）-α-D-glucan, and chitosan from Penicillium chrysongenum mycelium. First the mycelia are pretreated with 0.1mol·L^-1 of NaOH. After recovery by centrifugation the solid portion is made to undergo saponification and deacetylation reactaons by addition of 2mol·L^-1 NaOH and et anol.After reaction, extraction is carried out by addition of petroleum ether, which separates the reaction mixture into two phases. The upper layer of petroleum ether contains extracted ergosterol, and the .bottom layer of NaOH solution contains （1→3）-α-DEglucan; the chitosan is on the mycelia residuum. After isolation, the recovery yield of ergosterol is 0.52% of dry mycelium. That of （1→3）-α-D-glucan is about 8.2%; and chitosan is 5.7% with 86% deacetylation. The compositions have been characterized by 1R, HPLC analyses.展开更多
We evaluated the biomass and ergosterol content of Hericium erinaceus mycelium, and extracellular enzyme activities in H. erinaceus liquid culture following salicylic acid（SA） and methyl jasmonic acid（Me JA）supple...We evaluated the biomass and ergosterol content of Hericium erinaceus mycelium, and extracellular enzyme activities in H. erinaceus liquid culture following salicylic acid（SA） and methyl jasmonic acid（Me JA）supplementation. The optimal SA concentration was100 lmoláL-1, where the highest ergosterol content of 2.33 mgág-1was obtained following 6-day cultivation with100 lmoláL-1SA supplementation, and which was significantly higher than the unsupplemented control（p ／ 0.01）. Following 4-day supplementation with50 lmoláL-1Me JA, the highest ergosterol content obtained was 1.988 mgág-1, which was 25.8 % higher than the unsupplemented control. Our data indicate that SA and Me JA supplementation improves ergosterol content in H.erinaceus mycelium.展开更多
Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with ...Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with no previous record of anti-hepatocarcinoma activity.Methods:The anti-proliferative efficacy of the mushroom ethyl acetate extract was screened against a panel of seven cancer cell lines,namely Hep G2,MCF-7,MDA-MB-231,MAD-MB-436,MOLT-4,Reh,and K-562,and against peripheral blood mononuclear cells isolated from normal healthy donors by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay.The impact of the extract on nuclear morphology was examined by 40,6-diamidino-2-phenylindole staining and the apoptotic potential of the extract was evaluated through flow cytometry and Annexin V-PI dual staining,followed by an in vitro scratch assay to elucidate the anti-migratory potential of the extract.The apoptotic and antimigratory effects were further validated using in silico molecular docking with four compounds,ergosterol,ergosta-5,8-dien-3-ol,lanosterol,and eburicol,against two anti-apoptotic proteins,Bcl-2 and Bcl-XL,and two angiogenic receptors,VEGFR-1 and VEGFR-2.Results:The screening data revealed that ethyl acetate extract exhibited remarkable anti-proliferative efficacy against Hep G2 cells,with a half maximal inhibitory concentration(IC50)value of 263.53(8.09)mg/mL,followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mononuclear cells.A clear alteration of the cellular and nuclear morphology was concentration-dependently observed in Hep G2 cells.The extract induced robust apoptosis and a significant concentrationdependent increase in the scratch area.The results of in silico docking revealed that compared to standard drug sunitinib,both ergosterol and ergosta-5,8-dien-3-ol displayed lower binding energy,and satisfactory drugability and absorption,distribution,metabolism,excretion,and toxicity properties.Conclusions:T.heimii is a potential source for isolating lead anticancer molecules in the future.Ergosterol and ergosta-5,8-dien-3-ol hold great promise as new drugs against hepatocarcinoma.展开更多
In the present paper, the electrochemical behavior of ergosterol has been investigated by in situ circular dichroism (CD) spectroelectrochemistry with long path-length thin layer cell. E-0 (1.02V), alpha n(alpha) (0.3...In the present paper, the electrochemical behavior of ergosterol has been investigated by in situ circular dichroism (CD) spectroelectrochemistry with long path-length thin layer cell. E-0 (1.02V), alpha n(alpha) (0.302) of the electroxidation process of ergosterol were obtained from the CD spectroelectrochemical data. The mechanism of the electroxidation process of ergosterol is suggested.展开更多
Spectasterols F−O(1−10),ten interesting ergosterols with an aromatized B ring,were obtained from Aspergillus spectabilis.Their structures and absolute configurations were determined using a combination of high-resolut...Spectasterols F−O(1−10),ten interesting ergosterols with an aromatized B ring,were obtained from Aspergillus spectabilis.Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),nuclear magnetic resonance(NMR)spectroscopy,single-crystal X-ray diffraction analyses,and electronic circular dichroism(ECD)calculations.Structurally,these aromatic ergosterols feature versatile side chains.Notably,compound aromatic ergosterols featured versatile side chains,and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24.All compounds were evaluated for their neuroprotective activities,with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.展开更多
Although cellular sterol sensing and regulation of sterol biosynthesis are essential processes for eukaryotes,the mechanisms governing ergosterol homeostasis remain largely unknown in pathogenic fungi.In this study,we...Although cellular sterol sensing and regulation of sterol biosynthesis are essential processes for eukaryotes,the mechanisms governing ergosterol homeostasis remain largely unknown in pathogenic fungi.In this study,we identify the transcription factor Ff SR as a key regulator of sterol homeostasis in Fusarium fujikuroi,the causative agent of rice bakanae disease worldwide.Deletion of Ff SR results in reduced ergosterol levels,increasing the susceptibility of F.fujikuroi to azole fungicides.Mechanistically,azole-induced ergosterol depletion promotes Ff SR phase separation,which facilitates its binding to cis-elements at target promoters,subsequently activating the expression of ergosterol biosynthesis genes.Conversely,when ergosterol levels are high,ergosterol binds to Ff SR,inhibiting its phase separation and transcriptional activation.Additionally,we identify a natural compound,natamycin,as a direct inhibitor of Ff SR,suppressing its phase separation and transcriptional capability.These findings highlight a novel mechanism by which fungal pathogens regulate ergosterol homeostasis through transcription factor phase separation,indicating that small molecules targeting Ff SR could serve as a synergist to enhance azole efficacy against pathogenic Fusarium.展开更多
Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB ...Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB against Trichophyton rubrum which is the most common pathogens responsible for chronic dermatophytosis. Methods The minimum inhibitory concentration （MIC） ofAspidin BB against strains was determined by broth microdilution. The effects of Aspidin BB on ergosterol biosynthesis were investigated by content determination based on UPLC method. Besides, the effects of drugs on squalene epoxidase （SE） in T. rubrum cell membrane were analyzed. Results MIC value of Aspidin BB against T. rubrum was 25.0 IJg/mL. Aspidin BB reduced ergosterol content significantly, but no notable effect on squalene epoxidase activity. Conclusion The results suggested that Aspidin BB inhibited ergosterol biosynthesis. However, it was not squalene epoxidase but other components may sever as possible targets in ergosterol biosynthesis pathway.展开更多
Objective: Secondary metabolites and polyphenolic compounds from medicinal plants have been demonstrated to have multiple biological functions with promising research and development prospects. This study examined the...Objective: Secondary metabolites and polyphenolic compounds from medicinal plants have been demonstrated to have multiple biological functions with promising research and development prospects. This study examined the effect of β-stigmasterol(with ergosterol) and xylopic acid isolated from Anchomanes difformis on liver mitochondrial permeability transition pore(mPTP).Methods: The compounds were isolated by vacuum liquid chromatography. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions.Results:1H and13C NMR spectroscopic elucidation of the isolates affirmed the presence of β-stigmasterol with ergosterol(1:0.3) and xylopic acid. The isolates reversed the increase in lipid peroxidation and inhibited the opening of mitochondrial permeability transition pores caused by calcium and glucose.Pharmacological inhibition of m PTP offers a promising therapeutic target for the treatment of mitochondrial-associated disorders.Conclusion: Reduction in the activity of calcium ATPase and the expression of Caspase-3 and-9 were observed, suggesting that they could play a role in protecting physicochemical properties of membrane bilayers from free radical-induced severe cellular damage and be useful in the management of diseases where much apoptosis occurs.展开更多
Termites have physiological and behavioral immunities that make them highly resistant to pathogen infections,which complicates biocontrol efforts.However,the stimuli that trigger the pathogen-avoidance behaviors of te...Termites have physiological and behavioral immunities that make them highly resistant to pathogen infections,which complicates biocontrol efforts.However,the stimuli that trigger the pathogen-avoidance behaviors of termites are still unclear.Our study shows that workers of Coptotermes formosanus exposed to the conidia of Metarhizium anisopliae exhibited a significantly higher frequency and longer duration of allogrooming behaviors compared with untreated termites.Volatile compounds in the cuticle of control termites and termites previously exposed to a suspension of M.anisopliae conidia were analyzed and compared using a gas chromatography-mass spectrometer(GC-MS).Our results showed that the amount of ergosterol differed between the fungus-exposed and control termites.Choice tests showed that termites significantly preferred to stay on filter paper treated with ergosterol(0.05,0.1,or 1.0 mg/mL)compared with control filter paper.In addition,termites exposed to ergosterol followed by M.anisopliae conidia were allogroomed at a significantly higher frequency and for a longer duration than termites exposed to alcohol(the solvent used with the ergosterol in the ergosterol trials)alone followed by M.anisopliae conidia.These results showed that ergosterol may enhance the allogrooming behavior of termites in the presence of entomopathogenic fungi.展开更多
Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by opt...Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.展开更多
Agaricus bisporus mushrooms contain high levels of ergosterol(3–8 mg/g dw),which can be converted into vitamin D_(2)(VD2)under ultraviolet irradiation(UV).However,the photoconversion of ergosterol can also lead to th...Agaricus bisporus mushrooms contain high levels of ergosterol(3–8 mg/g dw),which can be converted into vitamin D_(2)(VD2)under ultraviolet irradiation(UV).However,the photoconversion of ergosterol can also lead to the production of inactive photoisomers decreasing the production yield of VD2.This study assesses the impact of UV irradiation conditions on the conversion of ergosterol into vitamin D2.The effects of various parameters were tested including the mushroom form(powder,extract,suspension),irradiation time(0–240 min),temperature(20–40℃),intensity(0.16–0.48 mW/cm^(2)),and agitation during UV-C irradiation.The mushroom extract was the most suitable mushroom form for VD_(2) production.Beyond VD_(2),other photoisomers(tachysterol and lumisterol),were detected through HPLC-APCI-MS and their levels increased with deep and prolonged irradiation.The highest VD_(2) levels(0.95–1.03 mg/g dw)were obtained by irradiating mushroom extracts with an intensity of 0.31 mW/cm^(2) for 10 min.These results highlight the potential of mushrooms for VD_(2) production through UV-C irradiation,which is accompanied by the formation of biologically-active photo-isomers.展开更多
Refined conversion factors for soil fungal biomarkers are proposed.High interspecific variability is present in all fungal biomarkers.A modeling approach supports the validity of biomarker estimates in diverse soils.I...Refined conversion factors for soil fungal biomarkers are proposed.High interspecific variability is present in all fungal biomarkers.A modeling approach supports the validity of biomarker estimates in diverse soils.ITS1 copies vary strongly,but are fungal-specific with least phylogenetic bias.A combination of fungal biomarkers will reveal soil fungal physiology and activity.The abundances of fungi and bacteria in soil are used as simple predictors for carbon dynamics,and represent widely available microbial traits.Soil biomarkers serve as quantitative estimates of these microbial groups,though not quantifying microbial biomass per se.The accurate conversion to microbial carbon pools,and an understanding of its comparability among soils is therefore needed.We refined conversion factors for classical fungal biomarkers,and evaluated the application of quantitative PCR(qPCR,rDNA copies)as a biomarker for soil fungi.Based on biomarker contents in pure fungal cultures of 30 isolates tested here,combined with comparable published datasets,we propose average conversion factors of 95.3 g fungal C g^(−1) ergosterol,32.0 mg fungal Cμmol−1 PLFA 18:2ω6,9 and 0.264 pg fungal C ITS1 DNA copy−1.As expected,interspecific variability was most pronounced in rDNA copies,though qPCR results showed the least phylogenetic bias.A modeling approach based on exemplary agricultural soils further supported the hypothesis that high diversity in soil buffers against biomarker variability,whereas also phylogenetic biases impact the accuracy of comparisons in biomarker estimates.Our analyses suggest that qPCR results cover the fungal community in soil best,though with a variability only partly offset in highly diverse soils.PLFA 18:2ω6,9 and ergosterol represent accurate biomarkers to quantify Ascomycota and Basidiomycota.To conclude,the ecological interpretation and coverage of biomarker data prior to their application in global models is important,where the combination of different biomarkers may be most insightful.展开更多
In yeast,the stress-responsive protein Whi2 interacts with phosphatase Psr1 to form a complex that regulates cell growth,reproduction,infection,and the stress response.However,the roles of Whi2 and Psr1 in Fusarium gr...In yeast,the stress-responsive protein Whi2 interacts with phosphatase Psr1 to form a complex that regulates cell growth,reproduction,infection,and the stress response.However,the roles of Whi2 and Psr1 in Fusarium graminearum remain unclear.In this study,we identified homologous genes of WHI2 and PSR1 in F.graminearum and evaluated their functions by constructing deletion mutants.By comparing the responses of the mutants to different stressors,we found that FgWHI2 and FgPSR1 were involved in responding to osmotic,cell wall and cell membrane stresses,while also affecting the sexual and asexual reproduction in F.graminearum.Our studies demonstrated that FgWHI2 and FgPSR1 regulate the biosynthesis of ergosterol and the transcriptional level of FgCYP51C,which is a CYP51 paralogues unique to Fusarium species.This study also found that the deoxynivalenol(DON)production of FgWHI2 and FgPSR1 deletion mutants was reduced by≥90%and DON production was positively correlated with the transcriptional levels of FgWHI2 and FgPSR1.In addition,we observed that FgWHI2 and FgPSR1 were involved in regulating the sensitivity of F.graminearum to chlorothalonil,fluazinam,azoxystrobin,phenamacril,and oligomycin.This study revealed cross-resistance between chlorothalonil and fluazinam.Meanwhile,chlorothalonil and fluazinam inhibited DON biosynthesis by altering the normal expression of FgWhi2 and FgPsr1.Interestingly,the subcellular localization of FgWhi2 and FgPsr1 was significantly altered after treatment with chlorothalonil and fluazinam,with increased co-localization.Collectively,these findings indicate that FgWHI2 and FgPSR1 play crucial roles in stress response mechanisms,reproductive processes,secondary metabolite synthesis,and fungicide sensitivity in F.graminearum.展开更多
The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechan...The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.展开更多
基金Supported by the National Natural Science Foundation of China （No.20636010, No.50373003, No.20406002）, Beijing Natural Science Foundation （No.2071002）, and the Special Funds for Major State Basic Research Program of China （973 Program, No.2007CB714305）.
文摘Abstract Ergosterol,（1→3）-α-D-glucan and chitosan are important biomaterials. In this research, a process has been developed to integratively extract ergosterol, （1→3）-α-D-glucan, and chitosan from Penicillium chrysongenum mycelium. First the mycelia are pretreated with 0.1mol·L^-1 of NaOH. After recovery by centrifugation the solid portion is made to undergo saponification and deacetylation reactaons by addition of 2mol·L^-1 NaOH and et anol.After reaction, extraction is carried out by addition of petroleum ether, which separates the reaction mixture into two phases. The upper layer of petroleum ether contains extracted ergosterol, and the .bottom layer of NaOH solution contains （1→3）-α-DEglucan; the chitosan is on the mycelia residuum. After isolation, the recovery yield of ergosterol is 0.52% of dry mycelium. That of （1→3）-α-D-glucan is about 8.2%; and chitosan is 5.7% with 86% deacetylation. The compositions have been characterized by 1R, HPLC analyses.
基金supported by funding from the China Agriculture Research System(CARS-24)the Heilongjiang Province Outstanding Youth Science Fund(JC201316)
文摘We evaluated the biomass and ergosterol content of Hericium erinaceus mycelium, and extracellular enzyme activities in H. erinaceus liquid culture following salicylic acid（SA） and methyl jasmonic acid（Me JA）supplementation. The optimal SA concentration was100 lmoláL-1, where the highest ergosterol content of 2.33 mgág-1was obtained following 6-day cultivation with100 lmoláL-1SA supplementation, and which was significantly higher than the unsupplemented control（p ／ 0.01）. Following 4-day supplementation with50 lmoláL-1Me JA, the highest ergosterol content obtained was 1.988 mgág-1, which was 25.8 % higher than the unsupplemented control. Our data indicate that SA and Me JA supplementation improves ergosterol content in H.erinaceus mycelium.
基金WB-DSTBT (West Bengal Department of Science and Technology and Biotechnology,Sanction No.:1158(Sanc)/ST BT-13015/15/2021-ST SEC dated 15/02/2022) for funding the projectCSIR (Council of Scientific and Industrial Research)+1 种基金UGC (University Grants Commission) for providing fellowship and contingency to individual research scholarsthe UGC-UPE and UGC-CAS programs at the Department of Botany,University of Calcutta for providing financial support
文摘Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with no previous record of anti-hepatocarcinoma activity.Methods:The anti-proliferative efficacy of the mushroom ethyl acetate extract was screened against a panel of seven cancer cell lines,namely Hep G2,MCF-7,MDA-MB-231,MAD-MB-436,MOLT-4,Reh,and K-562,and against peripheral blood mononuclear cells isolated from normal healthy donors by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay.The impact of the extract on nuclear morphology was examined by 40,6-diamidino-2-phenylindole staining and the apoptotic potential of the extract was evaluated through flow cytometry and Annexin V-PI dual staining,followed by an in vitro scratch assay to elucidate the anti-migratory potential of the extract.The apoptotic and antimigratory effects were further validated using in silico molecular docking with four compounds,ergosterol,ergosta-5,8-dien-3-ol,lanosterol,and eburicol,against two anti-apoptotic proteins,Bcl-2 and Bcl-XL,and two angiogenic receptors,VEGFR-1 and VEGFR-2.Results:The screening data revealed that ethyl acetate extract exhibited remarkable anti-proliferative efficacy against Hep G2 cells,with a half maximal inhibitory concentration(IC50)value of 263.53(8.09)mg/mL,followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mononuclear cells.A clear alteration of the cellular and nuclear morphology was concentration-dependently observed in Hep G2 cells.The extract induced robust apoptosis and a significant concentrationdependent increase in the scratch area.The results of in silico docking revealed that compared to standard drug sunitinib,both ergosterol and ergosta-5,8-dien-3-ol displayed lower binding energy,and satisfactory drugability and absorption,distribution,metabolism,excretion,and toxicity properties.Conclusions:T.heimii is a potential source for isolating lead anticancer molecules in the future.Ergosterol and ergosta-5,8-dien-3-ol hold great promise as new drugs against hepatocarcinoma.
文摘In the present paper, the electrochemical behavior of ergosterol has been investigated by in situ circular dichroism (CD) spectroelectrochemistry with long path-length thin layer cell. E-0 (1.02V), alpha n(alpha) (0.302) of the electroxidation process of ergosterol were obtained from the CD spectroelectrochemical data. The mechanism of the electroxidation process of ergosterol is suggested.
基金supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(No.U22A20380 and 82104043)+1 种基金the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Science and Technology Major Project of Hubei Province(No.2021ACA012).
文摘Spectasterols F−O(1−10),ten interesting ergosterols with an aromatized B ring,were obtained from Aspergillus spectabilis.Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),nuclear magnetic resonance(NMR)spectroscopy,single-crystal X-ray diffraction analyses,and electronic circular dichroism(ECD)calculations.Structurally,these aromatic ergosterols feature versatile side chains.Notably,compound aromatic ergosterols featured versatile side chains,and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24.All compounds were evaluated for their neuroprotective activities,with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.
基金supported by the National Natural Science Foundation of China(U21A20219 and 31930088)the National Key Research and Development Program of China(2022YFD1400100)China Agriculture Research System(CARS-03-29)。
文摘Although cellular sterol sensing and regulation of sterol biosynthesis are essential processes for eukaryotes,the mechanisms governing ergosterol homeostasis remain largely unknown in pathogenic fungi.In this study,we identify the transcription factor Ff SR as a key regulator of sterol homeostasis in Fusarium fujikuroi,the causative agent of rice bakanae disease worldwide.Deletion of Ff SR results in reduced ergosterol levels,increasing the susceptibility of F.fujikuroi to azole fungicides.Mechanistically,azole-induced ergosterol depletion promotes Ff SR phase separation,which facilitates its binding to cis-elements at target promoters,subsequently activating the expression of ergosterol biosynthesis genes.Conversely,when ergosterol levels are high,ergosterol binds to Ff SR,inhibiting its phase separation and transcriptional activation.Additionally,we identify a natural compound,natamycin,as a direct inhibitor of Ff SR,suppressing its phase separation and transcriptional capability.These findings highlight a novel mechanism by which fungal pathogens regulate ergosterol homeostasis through transcription factor phase separation,indicating that small molecules targeting Ff SR could serve as a synergist to enhance azole efficacy against pathogenic Fusarium.
基金Application-oriented Research Project of Guangdong Provincial Department of Science and Technology(2015B020234009)Traditional Chinese Medicine Industry Research Project of State Administration of Traditional Chinese Medicine of People’s Republic of China(201507004)
文摘Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB against Trichophyton rubrum which is the most common pathogens responsible for chronic dermatophytosis. Methods The minimum inhibitory concentration （MIC） ofAspidin BB against strains was determined by broth microdilution. The effects of Aspidin BB on ergosterol biosynthesis were investigated by content determination based on UPLC method. Besides, the effects of drugs on squalene epoxidase （SE） in T. rubrum cell membrane were analyzed. Results MIC value of Aspidin BB against T. rubrum was 25.0 IJg/mL. Aspidin BB reduced ergosterol content significantly, but no notable effect on squalene epoxidase activity. Conclusion The results suggested that Aspidin BB inhibited ergosterol biosynthesis. However, it was not squalene epoxidase but other components may sever as possible targets in ergosterol biosynthesis pathway.
文摘Objective: Secondary metabolites and polyphenolic compounds from medicinal plants have been demonstrated to have multiple biological functions with promising research and development prospects. This study examined the effect of β-stigmasterol(with ergosterol) and xylopic acid isolated from Anchomanes difformis on liver mitochondrial permeability transition pore(mPTP).Methods: The compounds were isolated by vacuum liquid chromatography. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions.Results:1H and13C NMR spectroscopic elucidation of the isolates affirmed the presence of β-stigmasterol with ergosterol(1:0.3) and xylopic acid. The isolates reversed the increase in lipid peroxidation and inhibited the opening of mitochondrial permeability transition pores caused by calcium and glucose.Pharmacological inhibition of m PTP offers a promising therapeutic target for the treatment of mitochondrial-associated disorders.Conclusion: Reduction in the activity of calcium ATPase and the expression of Caspase-3 and-9 were observed, suggesting that they could play a role in protecting physicochemical properties of membrane bilayers from free radical-induced severe cellular damage and be useful in the management of diseases where much apoptosis occurs.
基金supported by the GDAS Special Project of Science and Technology Development(2020GDASYL-20200103091)Guangdong Basic and Applied Basic Research Foundation(2020A1515110416)+1 种基金Science and Technology Planning Project of Guangzhou(202102021018)Science and Technology Planning Key Project of Guangzhou(201904020002)。
文摘Termites have physiological and behavioral immunities that make them highly resistant to pathogen infections,which complicates biocontrol efforts.However,the stimuli that trigger the pathogen-avoidance behaviors of termites are still unclear.Our study shows that workers of Coptotermes formosanus exposed to the conidia of Metarhizium anisopliae exhibited a significantly higher frequency and longer duration of allogrooming behaviors compared with untreated termites.Volatile compounds in the cuticle of control termites and termites previously exposed to a suspension of M.anisopliae conidia were analyzed and compared using a gas chromatography-mass spectrometer(GC-MS).Our results showed that the amount of ergosterol differed between the fungus-exposed and control termites.Choice tests showed that termites significantly preferred to stay on filter paper treated with ergosterol(0.05,0.1,or 1.0 mg/mL)compared with control filter paper.In addition,termites exposed to ergosterol followed by M.anisopliae conidia were allogroomed at a significantly higher frequency and for a longer duration than termites exposed to alcohol(the solvent used with the ergosterol in the ergosterol trials)alone followed by M.anisopliae conidia.These results showed that ergosterol may enhance the allogrooming behavior of termites in the presence of entomopathogenic fungi.
基金supported by the National Natural Science Foundation(81725020,82003591 and 81973175,China)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07-E00073,China)Science and Technology Commission of Shanghai Municipality(20S11900400,China)。
文摘Invasive fungal infections(IFIs)have been associated with high mortality,highlighting the urgent need for developing novel antifungal strategies.Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14a-demethylase(CYP51)inhibitors.The photocaged triazoles completely shielded the CYP51inhibition.The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4%and 83.7%,respectively.Importantly,the shielded antifungal activity(MIC80≥64μg/m L)could be efficiently recovered(MIC80=0.5—8μg/m L)by light irradiation.The new chemical tools enable optical control of fungal growth arrest,morphological conversion and biofilm formation.The ability for highprecision antifungal treatment was validated by in vivo models.The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model.Overall,this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.
基金grateful to the Marche Region(Italy)for the financial support for this research project(Project:FPI400060 Assegno COVID19 RM)to Lavermicocca Funghi Spa(Macerata,Italy)for providing mushrooms.
文摘Agaricus bisporus mushrooms contain high levels of ergosterol(3–8 mg/g dw),which can be converted into vitamin D_(2)(VD2)under ultraviolet irradiation(UV).However,the photoconversion of ergosterol can also lead to the production of inactive photoisomers decreasing the production yield of VD2.This study assesses the impact of UV irradiation conditions on the conversion of ergosterol into vitamin D2.The effects of various parameters were tested including the mushroom form(powder,extract,suspension),irradiation time(0–240 min),temperature(20–40℃),intensity(0.16–0.48 mW/cm^(2)),and agitation during UV-C irradiation.The mushroom extract was the most suitable mushroom form for VD_(2) production.Beyond VD_(2),other photoisomers(tachysterol and lumisterol),were detected through HPLC-APCI-MS and their levels increased with deep and prolonged irradiation.The highest VD_(2) levels(0.95–1.03 mg/g dw)were obtained by irradiating mushroom extracts with an intensity of 0.31 mW/cm^(2) for 10 min.These results highlight the potential of mushrooms for VD_(2) production through UV-C irradiation,which is accompanied by the formation of biologically-active photo-isomers.
基金funding by the Deutsche Forschungsgemeinschaft(DFG,grant number 465123751,SPP2322 SoilSystems)supported by DFG grant HE 6183/5-1 and SM by MA4436/1-5.
文摘Refined conversion factors for soil fungal biomarkers are proposed.High interspecific variability is present in all fungal biomarkers.A modeling approach supports the validity of biomarker estimates in diverse soils.ITS1 copies vary strongly,but are fungal-specific with least phylogenetic bias.A combination of fungal biomarkers will reveal soil fungal physiology and activity.The abundances of fungi and bacteria in soil are used as simple predictors for carbon dynamics,and represent widely available microbial traits.Soil biomarkers serve as quantitative estimates of these microbial groups,though not quantifying microbial biomass per se.The accurate conversion to microbial carbon pools,and an understanding of its comparability among soils is therefore needed.We refined conversion factors for classical fungal biomarkers,and evaluated the application of quantitative PCR(qPCR,rDNA copies)as a biomarker for soil fungi.Based on biomarker contents in pure fungal cultures of 30 isolates tested here,combined with comparable published datasets,we propose average conversion factors of 95.3 g fungal C g^(−1) ergosterol,32.0 mg fungal Cμmol−1 PLFA 18:2ω6,9 and 0.264 pg fungal C ITS1 DNA copy−1.As expected,interspecific variability was most pronounced in rDNA copies,though qPCR results showed the least phylogenetic bias.A modeling approach based on exemplary agricultural soils further supported the hypothesis that high diversity in soil buffers against biomarker variability,whereas also phylogenetic biases impact the accuracy of comparisons in biomarker estimates.Our analyses suggest that qPCR results cover the fungal community in soil best,though with a variability only partly offset in highly diverse soils.PLFA 18:2ω6,9 and ergosterol represent accurate biomarkers to quantify Ascomycota and Basidiomycota.To conclude,the ecological interpretation and coverage of biomarker data prior to their application in global models is important,where the combination of different biomarkers may be most insightful.
基金supported by the National Key Research and Development Program of China(2022YFD1400100)the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(21)2037)+1 种基金the Guidance Foundation of the Hainan Institute of Nanjing Agricultural University,China(NAUSY-MS03)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX20_0596)。
文摘In yeast,the stress-responsive protein Whi2 interacts with phosphatase Psr1 to form a complex that regulates cell growth,reproduction,infection,and the stress response.However,the roles of Whi2 and Psr1 in Fusarium graminearum remain unclear.In this study,we identified homologous genes of WHI2 and PSR1 in F.graminearum and evaluated their functions by constructing deletion mutants.By comparing the responses of the mutants to different stressors,we found that FgWHI2 and FgPSR1 were involved in responding to osmotic,cell wall and cell membrane stresses,while also affecting the sexual and asexual reproduction in F.graminearum.Our studies demonstrated that FgWHI2 and FgPSR1 regulate the biosynthesis of ergosterol and the transcriptional level of FgCYP51C,which is a CYP51 paralogues unique to Fusarium species.This study also found that the deoxynivalenol(DON)production of FgWHI2 and FgPSR1 deletion mutants was reduced by≥90%and DON production was positively correlated with the transcriptional levels of FgWHI2 and FgPSR1.In addition,we observed that FgWHI2 and FgPSR1 were involved in regulating the sensitivity of F.graminearum to chlorothalonil,fluazinam,azoxystrobin,phenamacril,and oligomycin.This study revealed cross-resistance between chlorothalonil and fluazinam.Meanwhile,chlorothalonil and fluazinam inhibited DON biosynthesis by altering the normal expression of FgWhi2 and FgPsr1.Interestingly,the subcellular localization of FgWhi2 and FgPsr1 was significantly altered after treatment with chlorothalonil and fluazinam,with increased co-localization.Collectively,these findings indicate that FgWHI2 and FgPSR1 play crucial roles in stress response mechanisms,reproductive processes,secondary metabolite synthesis,and fungicide sensitivity in F.graminearum.
基金supported by the National Natural Science Foundation of China(82460111)the The First People’s Hospital of Yunnan Province Talent Project program(No.KHBS-2022013,KHYJ-2025-04-02,2022-KHRCBZ-B03)+4 种基金the Kunming Medical University Joint Special Project on Applied Basic Research(202301AY070001-210)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04)Yunnan Foundmental basical research project(202301AT070034)the Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases(No.2022ZDKFKT001)the Open Project of Yunnan Provincial Clinical Medical Research Center for Elderly Diseases(No.:2023YJZX-LN03/13 of 202102AA3100692023).
文摘The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.
