Mycobiology

  • 제47권2호
  • /
  • Pages.207-216
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  • 2019
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  • 1229-8093(pISSN)
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  • 2092-9323(eISSN)
한국균학회 (The Korean Society of Mycology)
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AcuD Gene Knockout Attenuates the Virulence of Talaromyces marneffei in a Zebrafish Model

  • Feng, Jiao (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Chen, Zhiwen (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • He, Liya (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Xiao, Xing (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Chen, Chunmei (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Chu, Jieming (Johns Hopkins University Bloomberg School of Public Health) ;
  • Mylonakis, Eleftherios (Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University) ;
  • Xi, Liyan (Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University)
  • 투고 : 2018.10.13
  • 심사 : 2019.05.07
  • 발행 : 2019.06.01
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초록

Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at $28^{\circ}C$, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ${\Delta}AcuD$ was significantly attenuated in this Zebrafish infection model.

키워드

참고문헌

  1. Samson RA, Yilmaz N, Houbraken J. Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in Penicillium subgenus Biverticillium. Stud Mycol. 2011;70:159-183. https://doi.org/10.3114/sim.2011.70.04
  2. Le T, Wolbers M, Chi NH, et al. Epidemiology, seasonality, and predictors of outcome of AIDSassociated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis. 2011;52:945-952. https://doi.org/10.1093/cid/cir028
  3. Canovas D, Andrianopoulos A. Developmental regulation of the glyoxylate cycle in the human pathogen Penicillium marneffei. Mol Microbiol. 2006;62:1725-1738. https://doi.org/10.1111/j.1365-2958.2006.05477.x
  4. Xi L, Xu X, Liu W, et al. Differentially expressed proteins of pathogenic Penicillium marneffei in yeast and mycelial phases. J Med Microbiol. 2007;56:298-304. https://doi.org/10.1099/jmm.0.46808-0
  5. Li J, Xi LY, Liu HF, et al. Differential expression of isocitrate lyase in P. marneffei phagocytized by nonstimulated and stimulated murine macrophages. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27:631-633.
  6. Thirach S, Cooper CJ, Vanittanakom N. Molecular analysis of the Penicillium marneffei glyceraldehyde-3-phosphate dehydrogenase-encoding gene (gpdA) and differential expression of gpdA and the isocitrate lyase-encoding gene (acuD) upon internalization by murine macrophages. J Med Microbiol. 2008;57:1322-1328. https://doi.org/10.1099/jmm.0.2008/002832-0
  7. Dolan SK, Welch M. The glyoxylate shunt, 60 years on. Annu Rev Microbiol. 2018;72:309-330. https://doi.org/10.1146/annurev-micro-090817-062257
  8. Dunn MF, Ramirez-Trujillo JA, Hernandez-Lucas I. Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis. Microbiology (Reading, Engl). 2009;155:3166-3175. https://doi.org/10.1099/mic.0.030858-0
  9. Chew SY, Ho KL, Cheah YK, et al. Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata. Sci Rep. 2019;9:2843. https://doi.org/10.1038/s41598-019-39117-1
  10. Sun J, Li X, Feng P, et al. RNAi-mediated silencing of fungal acuD gene attenuates the virulence of Penicillium marneffei. Med Mycol. 2014;52:167-178. https://doi.org/10.1093/mmy/myt006
  11. Schobel F, Ibrahim-Granet O, Ave P, et al. Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of invasive aspergillosis. Infect Immun. 2007;75:1237-1244. https://doi.org/10.1128/IAI.01416-06
  12. Rude TH, Toffaletti DL, Cox GM, et al. Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus neoformans. Infect Immun. 2002;70:5684-5694. https://doi.org/10.1128/IAI.70.10.5684-5694.2002
  13. Lorenz MC, Fink GR. The glyoxylate cycle is required for fungal virulence. Nature. 2001;412:83-86. https://doi.org/10.1038/35083594
  14. Asakura M, Okuno T, Takano Y. Multiple contributions of peroxisomal metabolic function to fungal pathogenicity in Colletotrichum lagenarium. Appl Environ Microbiol. 2006;72:6345-6354. https://doi.org/10.1128/AEM.00988-06
  15. Wang ZY, Thornton CR, Kershaw MJ, et al. The glyoxylate cycle is required for temporal regulation of virulence by the plant pathogenic fungus Magnaporthe grisea. Mol Microbiol. 2003;47:1601-1612. https://doi.org/10.1046/j.1365-2958.2003.03412.x
  16. Idnurm A, Howlett BJ. Isocitrate lyase is essential for pathogenicity of the fungus Leptosphaeria maculans to canola (Brassica napus). Eukaryot Cell. 2002;1:719-724. https://doi.org/10.1128/EC.1.5.719-724.2002
  17. Borneman AR, Hynes MJ, Andrianopoulos A. The abaA homologue of Penicillium marneffei participates in two developmental programmes: conidiation and dimorphic growth. Mol Microbiol. 2000;38:1034-1047. https://doi.org/10.1046/j.1365-2958.2000.02202.x
  18. Chen C, Feng J, Chen Z, et al. Optimization of the protoplast-mediated transformation system of Penicillium marneffei. Chin J Mycol. 2016;3:140-144.
  19. Huang X, Li D, Xi L, et al. Caenorhabditis elegans: a simple nematode infection model for Penicillium marneffei. PLoS One. 2014;9:e108764. https://doi.org/10.1371/journal.pone.0108764
  20. Huang X, Li D, Xi L, et al. Galleria mellonella larvae as an infection model for Penicillium marneffei. Mycopathologia. 2015;180:159-164. https://doi.org/10.1007/s11046-015-9897-y
  21. Rosowski EE, Knox BP, Archambault LS, et al. The Zebrafish as a model host for invasive fungal infections. J Fungi (Basel). 2018;4:136. https://doi.org/10.3390/jof4040136
  22. Borneman AR, Hynes MJ, Andrianopoulos A. An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei complements the defect in sexual development of an Aspergillus nidulans steA mutant. Genetics. 2001;157:1003-1014. https://doi.org/10.1093/genetics/157.3.1003
  23. Xiao X, Feng J, Li Y, et al. Agrobacterium tumefaciens-mediated transformation: an efficient tool for targeted gene disruption in Talaromyces marneffei. World J Microbiol Biotechnol. 2017;33:183. https://doi.org/10.1007/s11274-017-2352-0
  24. Knox BP, Deng Q, Rood M, et al. Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae. Eukaryot Cell. 2014;13:1266-1277. https://doi.org/10.1128/EC.00080-14
  25. Rauta PR, Nayak B, Das S. Immune system and immune responses in fish and their role in comparative immunity study: a model for higher organisms. Immunol Lett. 2012;148:23-33. https://doi.org/10.1016/j.imlet.2012.08.003
  26. Howe DG, Bradford YM, Eagle A, et al. The Zebrafish Model Organism Database: new support for human disease models, mutation details, gene expression phenotypes and searching. Nucleic Acids Res. 2017;45:D758-D768. https://doi.org/10.1093/nar/gkw1116
  27. Raldua D, Pina B. In vivo zebrafish assays for analyzing drug toxicity. Expert Opin Drug Metab Toxicol. 2014;10:685-697. https://doi.org/10.1517/17425255.2014.896339
  28. Tavares B, Santos LS. The importance of Zebrafish in biomedical research. Acta Med Port. 2013;26:583-592.
  29. Simmich J, Staykov E, Scott E. Zebrafish as an appealing model for optogenetic studies. Prog Brain Res. 2012;196:145-162. https://doi.org/10.1016/B978-0-444-59426-6.00008-2
  30. Brothers KM, Newman ZR, Wheeler RT. Live imaging of disseminated candidiasis in zebrafish reveals role of phagocyte oxidase in limiting filamentous growth. Eukaryot Cell. 2011;10:932-944. https://doi.org/10.1128/EC.05005-11
  31. Tenor JL, Oehlers SH, Yang JL, et al. Live imaging of host-parasite interactions in a zebrafish infection model reveals cryptococcal determinants of virulence and central nervous system invasion. Mbio. 2015;6:e1415-e1425.
  32. Ellett F, Pazhakh V, Pase L, et al. Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo. PLoS Pathog. 2018;14:e1007063. https://doi.org/10.1371/journal.ppat.1007063
  33. van der Sar AM, Appelmelk BJ, Vandenbroucke-Grauls CM, et al. A star with stripes: zebrafish as an infection model. Trends Microbiol. 2004;12:451-457. https://doi.org/10.1016/j.tim.2004.08.001
  34. Bojarczuk A, Miller KA, Hotham R, et al. Cryptococcus neoformans intracellular proliferation and capsule size determines early macrophage control of infection. Sci Rep. 2016;6:21489. https://doi.org/10.1038/srep21489

피인용 문헌

  1. Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation vol.12, 2019, https://doi.org/10.3389/fimmu.2021.636623
  2. Extracellular Vesicles Derived From Talaromyces marneffei Yeasts Mediate Inflammatory Response in Macrophage Cells by Bioactive Protein Components vol.11, 2021, https://doi.org/10.3389/fmicb.2020.603183