Transcriptomic and metabolomic analysis of fludioxonil-induced stress response and resistance in the poplar leaf blight fungus (Alternaria alternata)

Abstract

The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.

Keywords

Alternaria alternate / Fludioxonil / Resistance mechanism / Fungicide resistance / Transcriptomics and metabolomics analysis

References

[1] AbrahamN, SchroeterKL, ZhuY, ChanJ, EvansN, KimberMS, CarereJ, ZhouT, SeahSYK. Structure-function characterization of an aldo-keto reductase involved in detoxification of the mycotoxin, deoxynivalenol. Sci Rep, 2022, 12(1): 14737

[2] Al-KhayriJM, RashmiR, ToppoV, CholePB, BanadkaA, SudheerWN, NagellaP, ShehataWF, Al-MssallemMQ, AlessaFM, AlmaghaslaMI, RezkAA. Plant secondary metabolites: the weapons for biotic stress management. Metabolites, 2023, 13(6): 716

[3] Aung TST (2009) Regulation of alpha-dioxygenase expression and functional analyses in salt-stressed Arabidopsis thaliana. https://summit.sfu.ca/item/9576

[4] BarskiOA, TipparajuSM, BhatnagarA. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification. Drug Metab Rev, 2008, 40(4): 553-624

[5] BeckermanJ, PalmerC, TedfordE, YpemaH. Fifty years of fungicide development, deployment, and future use. Phytopathology, 2023, 113(4): 694-706

[6] Boguszewska-Mańkowska D, Nykiel M, Zagdańska B (2015) Protein oxidation and redox regulation of proteolysis. Basic principles and clinical significance of oxidative stress. Rijeka, Croatia: IntechOpen 17–35. https://doi.org/10.5772/61182

[7] CaceresI, KhouryAA, KhouryRE, LorberS, OswaldIP, KhouryAE, AtouiA, PuelO, BaillyJD. Aflatoxin biosynthesis and genetic regulation: a review. Toxins, 2020, 12(3): 150

[8] CamposMD, FélixMDR, PatanitaM, MateratskiP, AlbuquerqueA, RibeiroJA, VarandaC. Defense strategies: the role of transcription factors in tomato-pathogen interaction. Biology, 2022, 11(2): 235

[9] ChenAL, LiuT, WangZ, ChenXP. Plant root suberin: a layer of defence against biotic and abiotic stresses. Front Plant Sci, 2022, 13: 1056008

[10] ChenAQ, MaoX, SunQH, WeiZX, LiJ, YouYL, ZhaoJQ, JiangGB, WuYN, WangLP, LiYS. Alternaria mycotoxins: an overview of toxicity, metabolism, and analysis in food. J Agric Food Chem, 2021, 69(28): 7817-7830

[11] ChenC, LiQ, WangQF, LuDH, ZhangH, WangJ, FuRT. Transcriptional profiling provides new insights into the role of nitric oxide in enhancing Ganoderma oregonense resistance to heat stress. Sci Rep, 2017, 7(1): 15694

[12] ChenK, LiGJ, BressanRA, SongCP, ZhuJK, ZhaoY. Abscisic acid dynamics, signaling, and functions in plants. J Integr Plant Biol, 2020, 62(1): 25-54

[13] ChenMB, ChouWKW, Al-LamiN, FaraldosJA, AllemannRK, CaneDE, ChristiansonDW. Probing the role of active site water in the sesquiterpene cyclization reaction catalyzed by aristolochene synthase. Biochemistry, 2016, 55(20): 2864-2874

[14] ChenWD, ZhangYQ. Regulation of aldo-keto reductases in human diseases. Front Pharmacol, 2012, 3: 35

[15] DandanW, YangC, YaoY, MaD, LinH, HaoL, XinW, YeK, SunM, YuleH, YangY, ZhuangZ. SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus. eLife, 2024

[16] da Fonseca-PereiraP, Monteiro-BatistaRC, AraújoWL, Nunes-NesiA. Harnessing enzyme cofactors and plant metabolism: an essential partnership. Plant J, 2023, 114(5): 1014-1036

[17] DaudaWP, MorumdaD, AbrahamP, AdetunjiCO, GhazanfarS, GlenE, AbrahamSE, PeterGW, OgraIO, IfeanyiUJ, MusaH, AzametiMK, ParayBA, GulnazA. Genome-wide analysis of cytochrome P450s of Alternaria species: evolutionary origin, family expansion and putative functions. J Fungi, 2022, 8(4): 324

[18] De GiorgiF, FumagalliM, SciettiL, FornerisF. Collagen hydroxylysine glycosylation: non-conventional substrates for atypical glycosyltransferase enzymes. Biochem Soc Trans, 2021, 49(2): 855-866

[19] DrewD, NorthRA, NagarathinamK, TanabeM. Structures and general transport mechanisms by the major facilitator superfamily (MFS). Chem Rev, 2021, 121(9): 5289-5335

[20] DuPL, FanR, ZhangNN, WuCY, ZhangYQ. Advances in integrated multi-omics analysis for drug-target identification. Biomolecules, 2024, 14(6): 692

[21] EneIV, BrunkeS, BrownAJP, HubeB. Metabolism in fungal pathogenesis. Cold Spring Harb Perspect Med, 2014, 4(12): a019695

[22] EricksonJE, StanoszGR, KrugerEL. Photosynthetic consequences of Marssonina leaf spot differ between two poplar hybrids. New Phytol, 2004, 161(2): 577-583

[23] FarahN, ChinVK, ChongPP, LimWF, LimCW, BasirR, ChangSK, LeeTY. Riboflavin as a promising antimicrobial agent? A multi-perspective review. Curr Res Microb Sci, 2022, 3: 100111

[24] FillingerS, AjouzS, NicotPC, LerouxP, BardinM. Functional and structural comparison of pyrrolnitrin- and iprodione-induced modifications in the class III histidine-kinase Bos1 of Botrytis cinerea. PLoS ONE, 2012, 7(8): e42520

[25] FranklinDA, HeYZ, LesliePL, TikunovAP, FengerN, MacDonaldJM, ZhangYP. p53 coordinates DNA repair with nucleotide synthesis by suppressing PFKFB3 expression and promoting the pentose phosphate pathway. Sci Rep, 2016, 6: 38067

[26] FürstMJLJ, BoonstraM, BandstraS, FraaijeMW. Stabilization of cyclohexanone monooxygenase by computational and experimental library design. Biotechnol Bioeng, 2019, 116(9): 2167-2177

[27] GrabkeA, Fernández-OrtuñoD, AmiriA, LiXP, PeresNA, SmithP, SchnabelG. Characterization of iprodione resistance in Botrytis cinerea from strawberry and blackberry. Phytopathology, 2014, 104(4): 396-402

[28] GulZ, TangZH, ArifM, YeZ. An insight into abiotic stress and influx tolerance mechanisms in plants to cope in saline environments. Biology, 2022, 11(4): 597

[29] Gyamfi D, Awuah EO, Owusu S (2019) Lipid metabolism: an overview. In: The molecular nutrition of fats. edited by Vinood B. Patel, School of Life Sciences, University of Westminster, London, United Kingdom. San Diego, CA: Academic Press, an imprint of Elsevier. 17–32. https://doi.org/10.1016/B978-0-12-811297-7.00002-0

[30] HajamYA, RaniR, GanieSY, SheikhTA, JavaidD, QadriSS, PramodhS, AlsulimaniA, AlkhananiMF, HarakehS, HussainA, HaqueS, ReshiMS. Oxidative stress in human pathology and aging: molecular mechanisms and perspectives. Cells, 2022, 11(3): 552

[31] HanJ, LuZT, ZhangHF, JiSD, LiuB, KongN, YangYF, XingBY, LiuZH. Biocontrol mechanisms of poplar leaf blight due to Nigrospora oryzae. Physiol Plant, 2024, 176(5): e14556

[32] HeQ, LiuYH, LiuDH, GuoMM. Integration of transcriptomic and proteomic approaches unveils the molecular mechanism of membrane disintegration in Escherichia coli O157: H7 with ultrasonic treatment. Sci Total Environ, 2021, 791: 148366

[33] HeR, WeiPZ, OdibaAS, GaoLL, UsmanS, GongXF, WangB, WangLQ, JinC, LuGT, FangWX. Amino sugars influence Aspergillus fumigatus cell wall polysaccharide biosynthesis, and biofilm formation through interfering galactosaminogalactan deacetylation. Carbohydr Polym, 2024, 324: 121511

[34] HeWJ, ZhangLM, YiSY, TangXL, YuanQS, GuoMW, WuAB, QuB, LiHP, LiaoYC. An aldo-keto reductase is responsible for Fusarium toxin-degrading activity in a soil Sphingomonas strain. Sci Rep, 2017, 7(1): 9549

[35] HuCH, WangPQ, ZhangPP, NieXM, LiBB, TaiL, LiuWT, LiWQ, ChenKM. NADPH oxidases: the vital performers and center hubs during plant growth and signaling. Cells, 2020, 9(2): 437

[36] HuaYH, WuCY, SargsyanK, LimC. Sequence-motif detection of NAD(P)-binding proteins: discovery of a unique antibacterial drug target. Sci Rep, 2014, 4: 6471

[37] HuangS, LuoL, WenBH, LiuXR, YuKF, ZhangM. Metabolic signatures of two scleractinian corals from the northern South China Sea in response to extreme high temperature events. Mar Environ Res, 2024, 198: 106490

[38] HuangY, MaHJ, YueYZ, ZhouTC, ZhuZY, WangC. Integrated transcriptomic and transgenic analyses reveal potential mechanisms of poplar resistance to Alternaria alternata infection. BMC Plant Biol, 2022, 22(1): 413

[39] HýskováV, BělonožníkováK, ČeřovskáN, RyšlaváH. HSP70 plays an ambiguous role during viral infections in plants. Biologia Plant, 2021, 65: 68-79

[40] IaniriG, BaroneG, PalmieriD, QuiqueroM, GaetaI, De CurtisF, CastoriaR. Transcriptomic investigation of the interaction between a biocontrol yeast, Papiliotrema terrestris strain PT22AV, and the postharvest fungal pathogen Penicillium expansum on apple. Commun Biol, 2024, 7(1): 359

[41] JainA, SarsaiyaS, SinghR, GongQH, WuQ, ShiJS. Omics approaches in understanding the benefits of plant-microbe interactions. Front Microbiol, 2024, 15: 1391059

[42] JanR, KhanM, AsafS, LubnaAS, KimKM. Bioactivity and therapeutic potential of kaempferol and quercetin: new insights for plant and human health. Plants, 2022, 11(19): 2623

[43] JangraA, ChaturvediS, SihagS, SharmaG, TiwariS, ChhokarV. Identification and functional characterization of a novel aldo-keto reductase from Aloe vera. Planta, 2023, 258(6): 107

[44] Janse van RensburgHC, LimamiAM, Van den EndeW. Spermine and spermidine priming against Botrytis cinerea modulates ROS dynamics and metabolism in Arabidopsis. Biomolecules, 2021, 11(2): 223

[45] KhanD, NileAH, TripathiA, BankaitisVA. Emerging prospects for combating fungal infections by targeting phosphatidylinositol transfer proteins. Int J Mol Sci, 2021, 22(13): 6754

[46] KoczykG, PawłowskaJ, MuszewskaA. Terpenoid biosynthesis dominates among secondary metabolite clusters in Mucoromycotina genomes. J Fungi, 2021, 7(4): 285

[47] KorolevN, MamievM, ZahaviT, EladY. Screening of Botrytis cinerea isolates from vineyards in Israel for resistance to fungicides. Eur J Plant Pathol, 2011, 129(4): 591-608

[48] KrishnanK, AskewDS. Endoplasmic reticulum stress and fungal pathogenesis. Fungal Biol Rev, 2014, 28(2–3): 29-35

[49] KumariS, KumarM, GaurNA, PrasadR. Multiple roles of ABC transporters in yeast. Fungal Genet Biol, 2021, 150: 103550

[50] LappK, VödischM, KrollK, StrassburgerM, KniemeyerO, HeinekampT, BrakhageAA. Characterization of the Aspergillus fumigatus detoxification systems for reactive nitrogen intermediates and their impact on virulence. Front Microbiol, 2014, 5: 469

[51] LealSMJr, VareechonC, CowdenS, CobbBA, LatgéJP, MomanyM, PearlmanE. Fungal antioxidant pathways promote survival against neutrophils during infection. J Clin Invest, 2012, 122(7): 2482-2498

[52] LewandowskaM, KeylA, FeussnerI. Wax biosynthesis in response to danger: its regulation upon abiotic and biotic stress. New Phytol, 2020, 227(3): 698-713

[53] LiS, ShaoZR, LuC, YaoJT, ZhouYD, DuanDL. Glutamate dehydrogenase functions in glutamic acid metabolism and stress resistance in Pyropia haitanensis. Molecules, 2021, 26(22): 6793

[54] LiangXX, NiuQC, KongJC, ZhaoXY, ZhangB, LiL, JiaoC, GaiYP. Role of antioxidant molecules in the oxidative stress response networks in the tangerine pathotype of Alternaria alternata. Agronomy, 2023, 13(11): 2735

[55] LiuJP, TangYJ, BaoJS, WangHK, ChenMY, PengFR, TanPP. Integrated microbiome and metabolomics analysis reveal a closer relationship between soil metabolites and bacterial community than fungal community in pecan plantations. Land Degrad Dev, 2023, 34(10): 2812-2824

[56] LiuYR, MaMX, TangY, HuangZQ, GuoYP, MaQG, ZhaoLH. A NADPH-dependent aldo/keto reductase is responsible for detoxifying 3-keto-deoxynivalenol to 3- epi-deoxynivalenol in Pelagibacterium halotolerans ANSP101. Foods, 2024, 13(7): 1064

[57] MapurangaJ, ChangJY, ZhangLR, ZhangN, YangWX. Fungal secondary metabolites and small RNAs enhance pathogenicity during plant-fungal pathogen interactions. J Fungi, 2022, 9(1): 4

[58] Martı́nezAT. Molecular biology and structure-function of lignin-degrading heme peroxidases. Enzyme Microb Technol, 2002, 30(4): 425-444

[59] Martin-MontalvoA, SunYN, Diaz-RuizA, AliA, GutierrezV, PalaciosHH, CurtisJ, SiendonesE, ArizaJ, AbulwerdiGA, SunXP, WangAX, PearsonKJ, FishbeinKW, SpencerRG, WangM, HanXL, Scheibye-KnudsenM, BaurJA, ShertzerHG, NavasP, VillalbaJM, ZouSG, BernierM, de CaboR. Cytochrome b5 reductase and the control of lipid metabolism and healthspan. NPJ Aging Mech Dis, 2016, 2: 16006

[60] MullisMM, RamboIM, BakerBJ, ReeseBK. Diversity, ecology, and prevalence of antimicrobials in nature. Front Microbiol, 2019, 10: 2518

[61] NoeltingMC, SisternaMN, SulyokM, AbbiatiNN, MolinaMC. Damage caused by Alternaria alternata to the quality and germination of amaranth seeds. Eur J Plant Pathol, 2022, 163(1): 193-202

[62] PanLY, ZhouJ, SunY, QiaoBX, WanT, GuoRQ, ZhangJ, ShanDQ, CaiYL. Comparative transcriptome and metabolome analyses of cherry leaves spot disease caused by Alternaria alternata. Front Plant Sci, 2023, 14: 1129515

[63] PapaharalambusCA, GriendlingKK. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med, 2007, 17(2): 48-54

[64] PignéS, ZykwinskaA, JanodE, CuenotS, KerkoudM, RauloR, Bataillé-SimoneauN, MarchiM, KwasiborskiA, N’GuyenG, MabilleauG, SimoneauP, GuillemetteT. A flavoprotein supports cell wall properties in the necrotrophic fungus Alternaria brassicicola. Fungal Biol Biotechnol, 2017, 4: 1

[65] PuntscherH, KüttML, SkrinjarP, MikulaH, PodlechJ, FröhlichJ, MarkoD, WarthB. Tracking emerging mycotoxins in food: development of an LC-MS/MS method for free and modified Alternaria toxins. Anal Bioanal Chem, 2018, 410(18): 4481-4494

[66] PusztahelyiT, HolbIJ, PócsiI. Secondary metabolites in fungus-plant interactions. Front Plant Sci, 2015, 6: 573

[67] RenF, YanDH, WuGH, SunXM, SongXY, LiRH. Distinctive gene expression profiles and effectors consistent with host specificity in two formae speciales of Marssonina brunnea. Front Microbiol, 2020, 11: 276

[68] ReynoudN, PetitJ, BresC, LahayeM, RothanC, MarionD, BakanB. The complex architecture of plant cuticles and its relation to multiple biological functions. Front Plant Sci, 2021, 12: 782773

[69] RosenbergT, KislioukT, CramerT, ShinderD, DruyanS, MeiriN. Embryonic heat conditioning induces TET-dependent cross-tolerance to hypothalamic inflammation later in life. Front Genet, 2020, 11: 767

[70] ShankarA, SharmaKK. Fungal secondary metabolites in food and pharmaceuticals in the era of multi-omics. Appl Microbiol Biotechnol, 2022, 106(9–10): 3465-3488

[71] SongXC, ZhaoQJ, ZhouAA, WenXD, LiM, LiRY, LiaoX, XuTZ. The antifungal effects of citral on Magnaporthe oryzae occur via modulation of chitin content as revealed by RNA-seq analysis. J Fungi, 2021, 7(12): 1023

[72] StadingR, ChuC, CouroucliX, LingappanK, MoorthyB. Molecular role of cytochrome P4501A enzymes inoxidative stress. Curr Opin Toxicol, 2020, 20–21: 77-84

[73] SudheeranPK, OvadiaR, GalsarkerO, MaozI, SelaN, MaurerD, FeygenbergO, Oren ShamirM, AlkanN. Glycosylated flavonoids: fruit’s concealed antifungal arsenal. New Phytol, 2020, 225(4): 1788-1798

[74] SunML, DaiPB, CaoZY, DongJG. Purine metabolism in plant pathogenic fungi. Front Microbiol, 2024, 15: 1352354

[75] SvartzG, MeijideF, CollCP. Effects of a fungicide formulation on embryo-larval development, metamorphosis, and gonadogenesis of the South American toad Rhinella arenarum. Environ Toxicol Pharmacol, 2016, 45: 1-7

[76] TaoYD, LiuY, WanXS, XuJ, FuDY, ZhangJZ. High and low temperatures differentially affect survival, reproduction, and gene transcription in male and female moths of Spodoptera frugiperda. Insects, 2023, 14(12): 958

[77] TauqeerHM, AliS, RizwanM, AliQ, SaeedR, IftikharU, AhmadR, FaridM, AbbasiGH. Phytoremediation of heavy metals by Alternanthera bettzickiana: growth and physiological response. Ecotoxicol Environ Saf, 2016, 126: 138-146

[78] ThakurM, BhattacharyaS, KhoslaPK, PuriS. Improving production of plant secondary metabolites through biotic and abiotic elicitation. J Appl Res Med Aromat Plants, 2019, 12: 1-12

[79] Then R (2007) Dihydropteroate synthase. xPharm: the comprehensive pharmacology reference, Elsevier, p 1−7. (ISBN 9780080552323) https://doi.org/10.1016/B978-008055232-3.60524-0

[80] TianF, LeeSY, WooSY, ChoiHY, HeoS, NahG, ChunHS. Transcriptomic responses of Aspergillus flavus to temperature and oxidative stresses during aflatoxin production. Sci Rep, 2021, 11(1): 2803

[81] TiwariS, ThakurR, ShankarJ. Role of heat-shock proteins in cellular function and in the biology of fungi. Biotechnol Res Int, 2015, 2015: 132635

[82] TrisoliniL, GambacortaN, GorgoglioneR, MontaruliM, LaeraL, ColellaF, VolpicellaM, De GrassiA, PierriCL. FAD/NADH dependent oxidoreductases: from different amino acid sequences to similar protein shapes for playing an ancient function. J Clin Med, 2019, 8(12): 2117

[83] VlasovaII. Peroxidase activity of human hemoproteins: keeping the fire under control. Molecules, 2018, 23(10): 2561

[84] WangMS, SunXP, YuDL, XuJP, ChungK, LiHY. Genomic and transcriptomic analyses of the tangerine pathotype of Alternaria alternata in response to oxidative stress. Sci Rep, 2016, 6: 32437

[85] WangRQ, WangYT, YaoWJ, GeWG, JiangTB, ZhouBR. Transcriptome sequencing and WGCNA reveal key genes in response to leaf blight in poplar. Int J Mol Sci, 2023, 24(12): 10047

[86] WangY, LiuDM, YinHY, WangHQ, CaoC, WangJY, ZhengJ, LiuJH. Transcriptomic and metabolomic analyses of the response of resistant peanut seeds to Aspergillus flavus infection. Toxins, 2023, 15(7): 414

[87] WangY, MostafaS, ZengW, JinB. Function and mechanism of jasmonic acid in plant responses to abiotic and biotic stresses. Int J Mol Sci, 2021, 22(16): 8568

[88] WhaleySG, ZhangQ, CaudleKE, David RogersP. Relative contribution of the ABC transporters Cdr1, Pdh1, and Snq2 to azole resistance in Candida glabrata. Antimicrob Agents Chemother, 2018, 62(10): e01070-e1118

[89] WitteTE, VillenueveN, ShieldsSW, SprouleA, EggertsonQ, KimNE, BoddyCN, DettmanJR, OveryDP. Untargeted metabolomics screening reveals unique secondary metabolite production from Alternaria section Alternaria. Front Mol Biosci, 2022, 9: 1038299

[90] XieLQ, DengZY, ZhangJ, DongHH, WangW, XingBH, LiuXR. Comparison of flavonoid O-glycoside, C-glycoside and their aglycones on antioxidant capacity and metabolism during in vitro digestion and in vivo. Foods, 2022, 11(6): 882

[91] XiongQ, ZhangLL, ZhengXY, QianYL, ZhangYX, ZhaoLJ, ChengQ. Rapid and specific detection of the poplar black spot disease caused by Marssonina brunnea using loop-mediated isothermal amplification assay. Plants, 2021, 10(2): 253

[92] YamaguchiS. Gibberellin metabolism and its regulation. Annu Rev Plant Biol, 2008, 59: 225-251

[93] YangS, TianZ, FengY, ZhangK, PanYC, LiY, WangZC, WeiWH, QiaoXC, ZhouRH, YanL, LiQ, GuoH, YuanJ, LiPC, LvZ. Transcriptomics and metabolomics reveal changes in the regulatory mechanisms of osteosarcoma under different culture methods in vitro. BMC Med Genomics, 2022, 15(1): 265

[94] YiYJ, LuanPY, FanMH, WuXQ, SunZK, ShangZJ, YangYZ, LiCW. Antifungal efficacy of Bacillus amyloliquefaciens ZK-9 against Fusarium graminearum and analysis of the potential mechanism of its lipopeptides. Int J Food Microbiol, 2024, 422: 110821

[95] Yin XY, Bose D, Kwon A, Hanks SC, Jackson AU, Stringham HM, Welch R, Oravilahti A, Silva LF, FinnGen, Locke AE, Fuchsberger C, Service SK, Erdos MR, Bonnycastle LL, Kuusisto J, Stitziel NO, Hall IM, Morrison J, Ripatti S, Palotie A, Freimer NB, Collins FS, Mohlke KL, Scott LJ, Fauman EB, Burant C, Boehnke M, Laakso M, Wen XQ (2022) Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk. Am J Hum Genet 109(10): 1727–1741. https://doi.org/10.1016/j.ajhg.2022.08.007

[96] YouYL, HuQH, LiuN, XuCJ, LuSN, XuTC, MaoX. Metabolite analysis of Alternaria mycotoxins by LC-MS/MS and multiple tools. Molecules, 2023, 28(7): 3258

[97] ZengP, GuoZH, XiaoXY, CaoX, PengC. Response to cadmium and phytostabilization potential of Platycladus orientalis in contaminated soil. Int J Phytoremediation, 2018, 20(13): 1337-1345

[98] ZhangM, ZhangYD, LiYC, BiY, MaoRY, YangYY, JiangQQ, PruskyD. Cellular responses required for oxidative stress tolerance of the necrotrophic fungus Alternaria alternata, causal agent of pear black spot. Microorganisms, 2022, 10(3): 621

[99] ZhangP, ZhuYQ, ZhouSJ. Comparative analysis of powdery mildew resistant and susceptible cultivated cucumber (Cucumis sativus L.) varieties to reveal the metabolic responses to Sphaerotheca fuliginea infection. BMC Plant Biol, 2021, 21(1): 24

[100] ZhangWC, ZhangMX, SunM, HuMH, YuMC, SunJS, ZhangXW, DuB. Metabolomics-transcriptomics joint analysis: unveiling the dysregulated cell death network and developing a diagnostic model for high-grade neuroblastoma. Front Immunol, 2024, 14: 1345734

[101] ZhangYF, HeW, YanDH. Histopathologic characterization of the process of Marssonina brunnea infection in poplar leaves. Can J for Res, 2018, 48(11): 1302-1310

[102] ZhaoH, JiangJ, LiKL, LiuGF. Populus simonii × Populus nigra WRKY70 is involved in salt stress and leaf blight disease responses. Tree Physiol, 2017, 37(6): 827-844

[103] ZhaoML, GeYC, ZhouCZ, LiuXW, WuB. Specialized metabolites of the fungal genus Phomopsis: structures, bioactivities and biosynthesis. Fitoterapia, 2023, 168: 105523

[104] ZhouY, KhanH, XiaoJB, CheangWS. Effects of arachidonic acid metabolites on cardiovascular health and disease. Int J Mol Sci, 2021, 22(21): 12029

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