Dihydroorotase MoPyr4 is required for development, pathogenicity, and autophagy in rice blast fungus.
Magnaporthe oryzae
Autophagy
Dihydroorotase
Pathogenicity
Pyrimidine nucleotide biosynthesis
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
29
03
2024
accepted:
06
07
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
Dihydroorotase (DHOase) is the third enzyme in the six enzymatic reaction steps of the endogenous pyrimidine nucleotide de novo biosynthesis pathway, which is a metabolic pathway conserved in both bacteria and eukaryotes. However, research on the biological function of DHOase in plant pathogenic fungi is very limited. In this study, we identified and named MoPyr4, a homologous protein of Saccharomyces cerevisiae DHOase Ura4, in the rice blast fungus Magnaporthe oryzae and investigated its ability to regulate fungal growth, pathogenicity, and autophagy. Deletion of MoPYR4 led to defects in growth, conidiation, appressorium formation, the transfer and degradation of glycogen and lipid droplets, appressorium turgor accumulation, and invasive hypha expansion in M. oryzae, which eventually resulted in weakened fungal pathogenicity. Long-term replenishment of exogenous uridine-5'-phosphate (UMP) can effectively restore the phenotype and virulence of the ΔMopyr4 mutant. Further study revealed that MoPyr4 also participated in the regulation of the Pmk1-MAPK signaling pathway, co-localized with peroxisomes for the oxidative stress response, and was involved in the regulation of the Osm1-MAPK signaling pathway in response to hyperosmotic stress. In addition, MoPyr4 interacted with MoAtg5, the core protein involved in autophagy, and positively regulated autophagic degradation. Taken together, our results suggested that MoPyr4 for UMP biosynthesis was crucial for the development and pathogenicity of M. oryzae. We also revealed that MoPyr4 played an essential role in the external stress response and pathogenic mechanism through participation in the Pmk1-MAPK signaling pathway, peroxisome-related oxidative stress response mechanism, the Osm1-MAPK signaling pathway and the autophagy pathway.
Identifiants
pubmed: 39010102
doi: 10.1186/s12964-024-01741-4
pii: 10.1186/s12964-024-01741-4
doi:
Substances chimiques
Fungal Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
362Subventions
Organisme : National Key Research and Development Program of China
ID : 2023YFD1400202-3
Organisme : National Natural Science Foundation of China
ID : 32370208
Organisme : National Natural Science Foundation of China
ID : 32270201
Informations de copyright
© 2024. The Author(s).
Références
Carrey EA. Phosphorylation, allosteric effectors and inter-domain contacts in CAD; their role in regulation of early steps of pyrimidine biosynthesis. Biochem Soc Trans. 1993;21:191–5.
pubmed: 8095470
doi: 10.1042/bst0210191
Evans DR, Guy HI. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway. J Biol Chem. 2004;279:33035–8.
pubmed: 15096496
doi: 10.1074/jbc.R400007200
Nara T, Hshimoto T, Aoki T. Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes. Gene. 2000;257:209–22.
pubmed: 11080587
doi: 10.1016/S0378-1119(00)00411-X
Wang WY, Cui JY, Ma H, Lu WQ, Huang J. Targeting pyrimidine metabolism in the era of precision cancer medicine. Front Oncol. 2021;11:684961.
pubmed: 34123854
pmcid: 8194085
doi: 10.3389/fonc.2021.684961
De Montigny J, Belarbi A, Hubert JC, Lacroute F. Structure and expression of the URA5 gene of Saccharomyces cerevisiae. Molec Gen Genet. 1989;215:455–62.
pubmed: 2651891
doi: 10.1007/BF00427043
Li GY, Li DH, Wang T, He SP. Pyrimidine biosynthetic enzyme CAD: its function, regulation, and diagnostic potential. IJMS. 2021;22:10253.
pubmed: 34638594
pmcid: 8508918
doi: 10.3390/ijms221910253
Li Y, Raushel FM. Inhibitors designed for the active site of dihydroorotase. Bioorg Chem. 2005;33:470–83.
pubmed: 16213543
doi: 10.1016/j.bioorg.2005.08.001
Christopherson RI, Schmalzl KJ, Szabados E, Goodridge RJ, Harsanyi MC, Sant ME, et al. Mercaptan and Dicarboxylate inhibitors of Hamster Dihydroorotasef. Biochemistry. 1989;28:463–70.
pubmed: 2565732
doi: 10.1021/bi00428a009
García-Bayona L, Garavito MF, Lozano GL, Vasquez JJ, Myers K, Fry WE, et al. De novo pyrimidine biosynthesis in the oomycete plant pathogen Phytophthora infestans. Gene. 2014;537:312–21.
pubmed: 24361203
doi: 10.1016/j.gene.2013.12.009
Dean R, Van Kan JAL, Pretorius ZA, Hammond-Kosack KE, Di Pietro A, Spanu PD, et al. The top 10 fungal pathogens in molecular plant pathology. Mol Plant Pathol. 2012;13:414–30.
pubmed: 22471698
pmcid: 6638784
doi: 10.1111/j.1364-3703.2011.00783.x
Spence C, Alff E, Johnson C, Ramos C, Donofrio N, Sundaresan V, et al. Natural rice rhizospheric microbes suppress rice blast infections. BMC Plant Biol. 2014;14:130.
pubmed: 24884531
pmcid: 4036093
doi: 10.1186/1471-2229-14-130
Jeon J, Park SY, Chi MH, Choi J, Park J, Rho H-S, et al. Genome-wide functional analysis of pathogenicity genes in the rice blast fungus. Nat Genet. 2007;39:561–5.
pubmed: 17353894
doi: 10.1038/ng2002
Dean RA, Talbot NJ, Ebbole DJ, Farman ML, Mitchell TK, Orbach MJ, et al. The genome sequence of the rice blast fungus Magnaporthe Grisea. Nature. 2005;434:980–6.
pubmed: 15846337
doi: 10.1038/nature03449
Couch BC, Kohn LM. A multilocus gene genealogy concordant with host preference indicates segregation of a new species, Magnaporthe oryzae, from M-grisea. Mycologia. 2002;94:683–93.
Hamer JE, Howard RJ, Chumley FG, Valent B. A mechanism for surface attachment in spores of a plant pathogenic fungus. Science. 1988;239:288–90.
pubmed: 17769992
doi: 10.1126/science.239.4837.288
Veneault-Fourrey C, Barooah M, Egan M, Wakley G, Talbot NJ. Autophagic fungal cell death is necessary for infection by the rice blast fungus. Science. 2006;312:580–3.
pubmed: 16645096
doi: 10.1126/science.1124550
Wilson RA, Talbot NJ. Under pressure: investigating the biology of plant infection by Magnaporthe oryzae. Nat Rev Microbiol. 2009;7:185–95.
pubmed: 19219052
doi: 10.1038/nrmicro2032
Khang CH, Berruyer R, Giraldo MC, Kankanala P, Park S-Y, Czymmek K, et al. Translocation of Magnaporthe oryzae effectors into rice cells and their subsequent cell-to-cell movement. Plant Cell. 2010;22:1388–403.
pubmed: 20435900
pmcid: 2879738
doi: 10.1105/tpc.109.069666
Li GT, Zhou XY, Xu JR. Genetic control of infection-related development in Magnaporthe oryzae. Curr Opin Microbiol. 2012;15:678–84.
pubmed: 23085322
doi: 10.1016/j.mib.2012.09.004
Zhou XY, Liu WD, Wang CF, Xu QJ, Wang Y, Ding SL, et al. A MADS-box transcription factor MoMcm1 is required for male fertility, microconidium production and virulence in Magnaporthe oryzae. Mol Microbiol. 2011;80:33–53.
pubmed: 21276092
doi: 10.1111/j.1365-2958.2011.07556.x
Park G, Bruno KS, Staiger CJ, Talbot NJ, Xu JR. Independent genetic mechanisms mediate turgor generation and penetration peg formation during plant infection in the rice blast fungus. Mol Microbiol. 2004;53:1695–707.
pubmed: 15341648
doi: 10.1111/j.1365-2958.2004.04220.x
Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36:1811–36.
pubmed: 28596378
pmcid: 5494474
doi: 10.15252/embj.201796697
Klionsky DJ, Cregg JM, Dunn WA, Emr SD, Sakai Y, Sandoval IV, et al. A unified nomenclature for yeast autophagy-related genes. Dev Cell. 2003;5:539–45.
pubmed: 14536056
doi: 10.1016/S1534-5807(03)00296-X
Noda NN, Inagaki F. Mechanisms of autophagy. Annu Rev Biophys. 2015;44:101–22.
pubmed: 25747593
doi: 10.1146/annurev-biophys-060414-034248
Wen X, Klionsky DJ. An overview of macroautophagy in yeast. J Mol Biol. 2016;428:1681–99.
pubmed: 26908221
pmcid: 4846508
doi: 10.1016/j.jmb.2016.02.021
Liu XH, Xu F, Snyder JH, Shi HB, Lu JP, Lin FC. Autophagy in plant pathogenic fungi. Semin Cell Dev Biol. 2016;57:128–37.
pubmed: 27072489
doi: 10.1016/j.semcdb.2016.03.022
Kershaw MJ, Talbot NJ. Genome-wide functional analysis reveals that infection-associated fungal autophagy is necessary for rice blast disease. Proc Natl Acad Sci USA. 2009;106:15967–72.
pubmed: 19717456
pmcid: 2747227
doi: 10.1073/pnas.0901477106
Liu XH, Lu JP, Lin FC. Autophagy during conidiation, conidial germination and turgor generation in Magnaporthe Grisea. Autophagy. 2007;3:472–3.
pubmed: 17495517
doi: 10.4161/auto.4339
Zhu X-M, Li L, Wu M, Liang S, Shi H-B, Liu X-H, et al. Current opinions on autophagy in pathogenicity of fungi. Virulence. 2019;10:481–9.
pubmed: 30475080
doi: 10.1080/21505594.2018.1551011
Lu JP, Cao HJ, Zhang LL, Huang PY, Lin FC. Systematic analysis of Zn2Cys6 transcription factors required for development and pathogenicity by high-throughput gene knockout in the rice blast fungus. Xu JR, editor. PLoS Pathog. 2014;10:e1004432.
Howard RJ, Ferrari MA, Roach DH, Money NP. Penetration of hard substrates by a fungus employing enormous turgor pressures. Proc Natl Acad Sci USA. 1991;88:11281–4.
pubmed: 1837147
pmcid: 53118
doi: 10.1073/pnas.88.24.11281
Sun L, Qian H, Wu M, Zhao W, Liu M, Wei Y, et al. A subunit of ESCRT-III, MoIst1, is involved in Fungal Development, pathogenicity, and Autophagy in Magnaporthe oryzae. Front Plant Sci. 2022;13:845139.
pubmed: 35463448
pmcid: 9021896
doi: 10.3389/fpls.2022.845139
Mittler R. ROS are good. Trends Plant Sci. 2017;22:11–9.
pubmed: 27666517
doi: 10.1016/j.tplants.2016.08.002
Li P, Zhao LL, Qi F, Htwe NMPS, Li QY, Zhang DW, et al. The receptor-like cytoplasmic kinase RIPK regulates broad-spectrum ROS signaling in multiple layers of plant immune system. Mol Plant. 2021;14:1652–67.
pubmed: 34129947
doi: 10.1016/j.molp.2021.06.010
Wang J-Y, Li L, Chai R-Y, Qiu H-P, Zhang Z, Wang Y-L, et al. Pex13 and Pex14, the key components of the peroxisomal docking complex, are required for peroxisome formation, host infection and pathogenicity-related morphogenesis in Magnaporthe oryzae. Virulence. 2019;10:292–314.
pubmed: 30905264
pmcid: 6527019
doi: 10.1080/21505594.2019.1598172
Jacob S, Foster AJ, Yemelin A, Thines E. High osmolarity glycerol (HOG) signalling in Magnaporthe oryzae: identification of MoYPD1 and its role in osmoregulation, fungicide action, and pathogenicity. Fungal Biology. 2015;119:580–94.
pubmed: 26058534
doi: 10.1016/j.funbio.2015.03.003
Turrà D, Segorbe D, Di Pietro A. Protein kinases in plant-pathogenic fungi: conserved regulators of infection. Annu Rev Phytopathol. 2014;52:267–88.
pubmed: 25090477
doi: 10.1146/annurev-phyto-102313-050143
Dixon KP, Xu JR, Smirnoff N, Talbot NJ. Independent signaling pathways regulate cellular turgor during hyperosmotic stress and appressorium-mediated plant infection by Magnaporthe Grisea. Plant Cell. 1999;11:2045–58.
pubmed: 10521531
pmcid: 144108
doi: 10.1105/tpc.11.10.2045
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021;17:1–382.
Liu XH, Liu TB, Lin FC. Methods in enzymology. Amsterdam: Elsevier; 2008. pp. 271–94.
Qi ZQ, Liu MX, Dong YH, Yang J, Zhang HF, Zheng XB, et al. Orotate phosphoribosyl transferase MoPyr5 is involved in uridine 5′-phosphate synthesis and pathogenesis of Magnaporthe oryzae. Appl Microbiol Biotechnol. 2016;100:3655–66.
pubmed: 26810198
doi: 10.1007/s00253-016-7323-0
Liu M-Y, Sun L-X, Qian H, Zhang Y-R, Zhu X-M, Li L, et al. De Novo Purine Nucleotide Biosynthesis pathway is required for development and pathogenicity in Magnaporthe oryzae. JoF. 2022;8:915.
pubmed: 36135640
pmcid: 9502316
doi: 10.3390/jof8090915
Zhu JJ, Thompson CB. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019;20:436–50.
pubmed: 30976106
pmcid: 6592760
doi: 10.1038/s41580-019-0123-5
Lu JP, Liu XH, Feng XX, Min H, Lin FC. An autophagy gene, MgATG5, is required for cell differentiation and pathogenesis in Magnaporthe oryzae. Curr Genet. 2009;55:461–73.
pubmed: 19629489
doi: 10.1007/s00294-009-0259-5
Guo JY, Teng X, Laddha SV, Ma S, Van Nostrand SC, Yang Y, et al. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in ras-driven lung cancer cells. Genes Dev. 2016;30:1704–17.
pubmed: 27516533
pmcid: 5002976
doi: 10.1101/gad.283416.116
Karsli Uzunbas G, Guo JY, Price S, Teng X, Laddha SV, Khor S, et al. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov. 2014;4:914–27.
pubmed: 24875857
pmcid: 4125614
doi: 10.1158/2159-8290.CD-14-0363
Chen W, Zhang LS, Zhang KQ, Zhou BS, Kuo ML, Hu SY, et al. Reciprocal regulation of autophagy and dNTP pools in human cancer cells. Autophagy. 2014;10:1272–84.
pubmed: 24905824
pmcid: 4203552
doi: 10.4161/auto.28954
Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, et al. A ubiquitin-like system mediates protein lipidation. Nature. 2000;408:488–92.
pubmed: 11100732
doi: 10.1038/35044114
Noda NN, Fujioka Y, Hanada T, Ohsumi Y, Inagaki F. Structure of the Atg12–Atg5 conjugate reveals a platform for stimulating Atg8–PE conjugation. EMBO Rep. 2013;14:206–11.
pubmed: 23238393
doi: 10.1038/embor.2012.208
Talbot NJ, Ebbole DJ, Hamer JE. Identification and characterization of MPG1, a gene involved in pathogenicity from the Rice Blast Fungus Magnaporthe Grisea. Plant Cell. 1993;5:1575.
pubmed: 8312740
pmcid: 160387
Yan Y, Wang H, Zhu S, Wang J, Liu X, Lin F, et al. The Methylcitrate cycle is required for development and virulence in the Rice Blast Fungus Pyricularia oryzae. MPMI. 2019;32:1148–61.
pubmed: 30933666
doi: 10.1094/MPMI-10-18-0292-R
Gao H-M, Liu X-G, Shi H-B, Lu J-P, Yang J, Lin F-C, et al. MoMon1 is required for vacuolar assembly, conidiogenesis and pathogenicity in the rice blast fungus Magnaporthe oryzae. Res Microbiol. 2013;164:300–9.
pubmed: 23376292
doi: 10.1016/j.resmic.2013.01.001
Liu X-H, Ning G-A, Huang L-Y, Zhao Y-H, Dong B, Lu J-P, et al. Calpains are involved in asexual and sexual development, cell wall integrity and pathogenicity of the rice blast fungus. Sci Rep. 2016;6:31204.
pubmed: 27502542
pmcid: 4977516
doi: 10.1038/srep31204
Lu J-P, Feng X-X, Liu X-H, Lu Q, Wang H-K, Lin F-C. Mnh6, a nonhistone protein, is required for fungal development and pathogenicity of Magnaporthe Grisea. Fungal Genet Biol. 2007;44:819–29.
pubmed: 17644013
doi: 10.1016/j.fgb.2007.06.003
Purdue PE, Lazarow PB. Pex18p is constitutively degraded during peroxisome Biogenesis. J Biol Chem. 2001;276:47684–9.
pubmed: 11590152
doi: 10.1074/jbc.M106823200
Wang J, Zhang Z, Wang Y, Li L, Chai R, Mao X et al. PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae. Zhang Z, editor. PLoS ONE. 2013;8:e55554.