CcAbl1 is required for virulence via regulating NADPH–glutathione-mediated redox balance in Cytospora chrysosperma

Abstract

To counteract the reactive oxygen species (ROS) derived from host plants, pathogenic fungi employ various strategies to overcome ROS or balance redox homeostasis. Glucose metabolism is vital for fungi and provides NADPH for antioxidation, but the molecular features linking glucose metabolism and redox homeostasis in fungi remain elusive. In this study, we demonstrate that CcAbl1 is indispensable for the maintenance of glucose metabolism, redox homeostasis and pathogenicity in Cytospora chrysosperma. Loss of CcAbl1 severely compromises glucose utilization, disrupts carbohydrate metabolic pathways, markedly reduces intracellular NADPH levels and virulence. Furthermore, we provided evidence how CcAbl1 is involved in glucose utilization, NADPH balance, glutathione biosynthesis, and oxidative stress tolerance. These results demonstrate that CcAbl1 links virulence to NADPH and glutathione to maintain redox homeostasis in C. chrysosperma.

Keywords

Cytospora chrysosperma / Carbohydrate metabolism / NADPH-glutathione homeostasis / Redox balance / Oxidative stress tolerance / Pathogenicity

References

[1] Aburto C, Ruminot I, San Martin A. Acute stimulation of glucose metabolism by H₂O₂ sustains the NADPH steady-state under oxidative stress. Redox Biol, 2025, 85: 103740

[2] Andor A, Mohanraj M, Pato ZA, Uri K, Biri-Kovacs B, Cheng Q, Arner ESJ. TXNL1 has dual functions as a redox active thioredoxin-like protein as well as an ATP - and redox - independent chaperone. Redox Biol, 2023, 67: 15

[3] Black B, Silva LBRD, Hu G, Qu X, Smith DFQ, Magaña AA, Horianopoulos LC, Caza M, Attarian R, Foster LJ, Casadevall A, Kronstad JW. Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence. Nat Microbiol, 2024, 9(8): 2084-2098

[4] Bomble P, Nath BB. Differential manifestation of RONS and antioxidant enzymes in response to singular versus combinatorial stress in Chironomus ramosus. Stress Biol, 2022, 2(1): 14

[5] Cassier-Chauvat C, Marceau F, Farci S, Ouchane S, Chauvat F. The glutathione system : a journey from Cyanobacteria to higher eukaryotes. Antioxidants, 2023, 12(6): 32

[6] Castro B, Citterico M, Kimura S, Stevens DM, Wrzaczek M, Coaker G. Stress-induced reactive oxygen species compartmentalization, perception and signalling. Nat Plants, 2021, 7(4): 403-412

[7] Cui X, Zhang D, Gao L, Liu N, Lian S, Ren W, Li B, Wang C. β-Glucosidase VmGlu1 is required for toxin production and pathogenicity of Valsa mali. Phytopathology Res, 2025, 7(1): 12

[8] Ding Y, Yan B, Zhao S, Chen Y, Wan H, Qian W. Synthetic modulation of ROS scavenging during host - Sclerotinia sclerotiorum interaction : a new strategy for the development of highly resistant plants. Phytopathol Res, 2024, 6(1): 13

[9] Dorion S, Ouellet JC, Rivoal J. Glutathione metabolism in plants under stress: beyond reactive oxygen species detoxification. Metabolites, 2021, 11(9): 641

[10] Feng H, Xu M, Gao Y, Liang J, Guo F, Guo Y, Huang L. Vm-milR37 contributes to pathogenicity by regulating glutathione peroxidase gene VmGP in Valsa mali. Mol Plant Pathol, 2021, 22(2): 243-254

[11] Fernandes PAR, Coimbra MA. The antioxidant activity of polysaccharides : a structure-function relationship overview. Carbohydr Polym, 2023, 314: 15

[12] Fernandez J, Wright JD, Hartline D, Quispe CF, Madayiputhiya N, Wilson RA. Principles of carbon catabolite repression in the rice blast fungus : Tps1, Nmr1-3, and a MATE - family pump regulate glucose metabolism during infection. PLoS Genet, 2012, 8(5): 29

[13] Guo Y, Yao S, Yuan T, Wang Y, Zhang D, Tang W. The spatiotemporal control of KatG2 catalase-peroxidase contributes to the invasiveness of Fusarium graminearum in host plants. Mol Plant Pathol, 2019, 20(5): 685-700

[14] Han Y, Xu T, Chen H, Tang M. Sugar metabolism and 14-3-3 protein genes expression induced by arbuscular mycorrhizal fungi and phosphorus addition to response drought stress in Populus cathayana. J Plant Physiol, 2023, 288: 154075-154075

[15] Hristov BD. The role of glutathione metabolism in chronic illness development and its potential use as a novel therapeutic target. Cureus, 2022, 14(9): e29696

[16] Ju Y, Zhang Y, Tian X, Zhu N, Zheng Y, Qiao Y, Yang T, Niu B, Li X, Yu L, Liu Z, Wu Y, Zhi Y, Dong Y, Xu Q, Yang X, Wang X, Wang X, Deng H, Mao Y, Li X. Protein S-glutathionylation confers cellular resistance to ferroptosis induced by glutathione depletion. Redox Biol, 2025, 83: 103660

[17] Kang J, Bishayee K, Huh S. Azoxystrobin impairs neuronal migration and induces ROS dependent apoptosis in cortical neurons. Int J Mol Sci, 2021, 22(22): 12495

[18] Kim D, Kesavan R, Ryu K, Dey T, Marckx A, Menezes C, Praharaj PP, Morley S, Ko B, Soflaee MH, Tom HJ, Brown H, Vu HS, Tso S, Brautigam CA, Lemoff A, Mettlen M, Mishra P, Cai F, Allen DK, Hoxhaj G. Mitochondrial NADPH fuels mitochondrial fatty acid synthesis and lipoylation to power oxidative metabolism. Nat Cell Biol, 2025, 27(5): 790-800

[19] Lastdrager J, Hanson J, Smeekens S. Sugar signals and the control of plant growth and development. J Exp Bot, 2014, 65(3): 799-807

[20] Li M, Liu X, Wu F, Shi X, Kong D, Li X, Mu C, Qu D, Wang L, Su H. Fermentation broth of a novel endophytic fungus enhanced maize salt tolerance by regulating sugar metabolism and phytohormone biosynthesis or signaling. Plant Physiol Biochem, 2024, 216: 109125

[21] Li Q, Guo R, Li A, Wang Y. Roles of NADPH oxidases in regulating redox homeostasis and pathogenesis of the poplar canker fungus Cytospora chrysosperma. Stress Biol, 2025, 5(1): 33

[22] Lin L, Fan XL, Groenewald JZ, Jami F, Wingfield MJ, Voglmayr H, Jaklitsch W, Castlebury LA, Tian CM, Crous PW. Cytospora: an important genus of canker pathogens. Stud Mycol, 2024, 109: 323-401

[23] Liu Y, Li B, Chen T, Tian S, Zhang Z. The synthesis, degradation and biological function of trehalose-6-phosphate. Stress Biol, 2025, 5(1): 38-38

[24] Marroquin-Guzman M, Sun G, Wilson RA. Glucose-ABL1-TOR signaling modulates cell cycle tuning to control terminal appressorial cell differentiation. PLoS Genet, 2017, 13(1): e1006557

[25] Meng Y, Xiao Y, Zhu S, Xu L, Huang L. VmSpm1: a secretory protein from Valsa mali that targets apple's abscisic acid receptor MdPYL4 to suppress jasmonic acid signaling and enhance infection. New Phytol, 2024, 244(6): 2489-2504

[26] Miao Y, Tenor JL, Toffaletti DL, Maskarinec SA, Liu J, Lee RE, Perfect JR, Brennan RG. Structural and in vivo studies on trehalose-6-phosphate synthase from pathogenic fungi provide insights into Its catalytic mechanism, biological necessity, and potential for novel antifungal drug design. Mbio, 2017, 8(4): 10-1128

[27] Qiao J, Yu Z, Zhou H, Wang W, Wu H, Ye J. The pentose phosphate pathway : from mechanisms to implications for gastrointestinal cancers. Int J Mol Sci, 2025, 26(2): 26

[28] Ryder LS, Dagdas YF, Mentlak TA, Kershaw MJ, Thornton CR, Schuster M, Chen J, Wang Z, Talbot NJ. NADPH oxidases regulate septin-mediated cytoskeletal remodeling during plant infection by the rice blast fungus. Proc Natl Acad Sci U S A, 2013, 110(8): 3179-3184

[29] Sachdev S, Ansari SA, Ansari MI, Fujita M, Hasanuzzaman M. Abiotic stress and reactive oxygen species : generation , signaling , and defense mechanisms. Antioxidants, 2021, 10(2): 37

[30] Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol, 2020, 21(7): 363-383

[31] Sun G, Xia Y, Li K, Zhu Q, Ding F, Gu H, Zhang Z, Li X, Mi X, Chen J, Yao R, Zhang S, Ouyang H, Chen X, Liu T, Jiang H, Zhao Y, Qiu M, Ye W, Duan K, Ma Z, Dong S, Yin H, Wang Y, Wang Y. Dual activation of soybean resistance against Phytophthora sojae by pectin lyase and degraded pectin oligosaccharides. Sci China Life Sci, 2024, 67(12): 2746-2760

[32] TeSlaa T, Ralser M, Fan J, Rabinowitz JD. The pentose phosphate pathway in health and disease. Nat Metab, 2023, 5(8): 1275-1289

[33] Van Leemputte F, Vanthienen W, Wijnants S, Van Zeebroeck G, Thevelein JM. Aberrant intracellular pH regulation limiting glyceraldehyde - 3-phosphate dehydrogenase activity in the glucose-sensitive yeast tps1Δ mutant. Mbio, 2020, 11(5): 18

[34] Wen X, Li H, Li J, Mapuranga J, Zhang N, Song L, Chang J, Li R, Zhang Y, Liu D, Yang W (2025) The Puccinia triticina effector Pt3372 suppresses wheat innate immunity by targeting wheat TaERP3 in TcLr2a and TcLr18. Phytopathol Res 7(1):15. https://doi.org/10.1186/s42483-025-00332-6

[35] Wilson RA, Jenkinson JM, Gibson RP, Littlechild JA, Wang Z, Talbot NJ. Tps1 regulates the pentose phosphate pathway, nitrogen metabolism and fungal virulence. EMBO J, 2007, 26(15): 3673-3685

[36] Wilson RA, Gibson RP, Quispe CF, Littlechild JA, Talbot NJ. An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus. Proc Natl Acad Sci U S A, 2010, 107(50): 21902-21907

[37] Xie D, Tang C, Wang Y, Jin H, Wang Y (2023) The Transcription Factor CcRlm1 Regulates Cell Wall Maintenance and Poplar Defense Response by Directly Targeting CcChs6 and CcGna1 in Cytospora chrysosperma. Appl Environ Microbiol 89:e0066123. https://doi.org/10.1128/aem.00661-23

[38] Xu Z, Xiong D, Han Z, Tian C. A putative effector CcSp84 of Cytospora chrysosperma localizes to the plant nucleus to trigger plant immunity. Int J Mol Sci, 2022, 23(3): 14

[39] Xu S, Li Q, Jin H, Li A, Wang Y. Trehalose biosynthetic genes are involved in the development and pathogenesis in the poplar canker fungus Cytospora chrysosperma. Phytopathology, 2025, 115(3): 260-268

[40] Yamada K, Mine A. Sugar coordinates plant defense signaling. Sci Adv, 2024, 10(4): eadk4131-eadk4131

[41] Yang SL, Yu P, Chung K. The glutathione peroxidase-mediated reactive oxygen species resistance, fungicide sensitivity and cell wall construction in the citrus fungal pathogen Alternaria alternata. Environ Microbiol, 2016, 18(3): 923-935

[42] Yin Z, Liu H, Li Z, Ke X, Dou D, Gao X, Song N, Dai Q, Wu Y, Xu JR, Kang Z, Huang L. Genome sequence of Valsa canker pathogens uncovers a potential adaptation of colonization of woody bark. New Phytol, 2015, 208(4): 1202-1216

[43] Yuan P, Qian W, Jiang L, Jia C, Ma X, Kang Z, Liu J. A secreted catalase contributes to Puccinia striiformis resistance to host-derived oxidative stress. Stress Biol, 2021, 1(1): 22-22

[44] Zeng S, Yang R, Ming Z, Li A. The two-component system RstB / RstA regulates virulence through the Fe³⁺ -siderophore transport operon lpfetABC in the poplar canker bacterium Lonsdalea populi. Phytopathol Res, 2025, 7(1): 14

[45] Zhang F, Chen S, Zhang C, Wang Z, Miao J, Dai T, Hao J, Liu X. PsDMAP1/PsTIP60-regulated H4K16ac is required for ROS-dependent virulence adaptation of Phytophthora sojae on host plants. Proc Natl Acad Sci, 2024, 122(1): e2413127122

[46] Zhang H, Shen X, Shen W, Zhang D, Huang X, Zhu K, Liu J, Li G. Glutathione peroxidase LtGPX3 contributes to oxidative stress tolerance, virulence, and plant defense suppression in the peach gummosis fungus Lasiodiplodia theobromae. Phytopathology Res, 2024, 6(1): 15

[47] Zhang N, Lv F, Qiu F, Han D, Xu Y, Liang W (2023) Pathogenic fungi neutralize plant‐derived ROS via Srpk1 deacetylation. Embo J 42(9):EMBJ2022112634. https://doi.org/10.15252/embj.2022112634

[48] Zhao X, Wang Y, Yuan B, Zhao H, Wang Y, Tan Z, Wang Z, Wu H, Li G, Song W, Gupta R, Tsuda K, Ma Z, Gao X, Gu Q. Temporally-coordinated bivalent histone modifications of BCG1 enable fungal invasion and immune evasion. Nat Commun, 2024, 15(1): 231

[49] Zhu J, Schworer S, Berisa M, Kyung YJ, Ryu KW, Yi J, Jiang X, Cross JR, Thompson CB. Mitochondrial NADP (H) generation is essential for proline biosynthesis. Science, 2021, 372(6545): 968

Funding

National Key R&D Program of China(2022YFD1401000)

Fundamental Research Funds for the Central Universities(QNTD202510)

RIGHTS & PERMISSIONS

The Author(s)