Inference of Aspergillus fumigatus Pathways by Computational Genome Analysis: Tricarboxylic Acid Cycle (TCA) and Glyoxylate Shunt

  • Do, Jin-Hwan (Bioinformatics Group, School of Biological Sciences, University of Manchester) ;
  • Anderson, Michael-J. (The School of Medicine, University of Manchester) ;
  • Denning, David-W. (The School of Medicine, University of Manchester) ;
  • Erich, Bornberg-Bauer (Bioinformatics Group, School of Biological Sciences, University of Manchester)
  • Published : 2004.02.01

Abstract

Aspergillus fumigatus is one of the most common fungi in the human environment, both in-doors and out-doors. It is the main causative agent of invasive aspergillosis, a life-threatening mycosis among immunocompromised patients. The genome has been sequenced by an international consortium, including the Wellcome Trust Sanger Institute (U.K.) and The Institute for Genomic Research (TIGR, U.S.A.), and a ten times whole genome shotgun sequence assembly has been made publicly available. In this study, we identified tricarboxylic acid (TCA) cycle enzymes of A. fumigatus by comparative analysis with four other fungal species. The open reading frames showed high amino acid sequence similarity with the other fungal citric acid enzymes and well-conserved functional domains. All genes present in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans, and Neurospora crassa were also found in A. fumigatus. In addition, we identified four A. fumigatus genes coding for enzymes in the glyoxylate shunt, which may be required for fungal virulence. The architecture of multi-gene encoded enzymes, such as isocitrate dehydrogenase, 2-ketoglutarate, succinyl-CoA synthetase, and succinate dehydrogenase was well conserved in A. fumigatus. Furthermore, our results show that genes of A. fumigatus can be detected reliably using GlimmerM.

Keywords

References

  1. Anderson, M. J., S. Fröls, E. J. Prebble, and D. W. Denning. 2001. A comparative study of Aspergillus fumigatus genes. Fungal Genetics Newsletter 48: 79S. Abstract no. 163
  2. Beauvais, A., J. M. Bruneau, P. C. Mol, M. J. Buitrago, R. Legrand, and J. P. Latgé. 2001. Glucan synthase complex of Aspergillus fumigatus. J. Bacteriol. 183(1): 2273-2279
  3. Brakhage, A. A. and K. Langfelder. 2002. Menacing mold: The molecular biology of Aspergillus fumigatus. Annu. Rev. Microbiol. 56: 433-455
  4. Bullis, B. L. and B. D. Lemire. 1994. Isolation and characterization of the Saccharomyces cerevisiae SDH4 gene encoding a membrane anchor subunit of succinate dehydrogenase. J. Biol. Chem. 269: 6543-6549
  5. Chapman, K. B., S. D. Solomon, and J. D. Boeke. 1992. SDH1, the gene encoding the succinate dehydrogenase flavoprotein subunit from Saccharomyces cerevisiae. Gene 118: 131-136
  6. Cupp, J. R. and L. McAlister-Henn. 1991. NAD(+)-dependent iso-citrate dehydrogenase: Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. J. Biol. Chem. 266: 22199-22205
  7. Cupp, J. R. and L. McAlister-Henn. 1992. Cloning and characterization of the gene encoding the IDH1 subunit of NAD (+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae. J. Biol. Chem. 267: 16417- 16423
  8. Daignan-Fornier, B., M. Valens, B. D. Lemire, and M. Bolotin-Fukuhara. 1994. Structure and regulation of SDH3, the yeast gene encoding the cytochrome b560 subunit of respiratory complex II. J. Biol. Chem. 269: 15469-15472
  9. Denning, D. W., M. J. Anderson, G. Turner, J. P. Latgé, and J. W. Bennett. 2002. Sequencing the Aspergillus fumigatus genome. Lancet Infect. Dis. 2: 251-253
  10. Deutsch, M. and M. Long. 1999. Intron-exon structures of eukaryotic model organisms. Nucleic Acids Res. 27: 3219- 3228
  11. Gangloff, S. P., D. Margueret, and G. J.-M. Lauquin. 1990. Molecular cloning of the yeast mitochondrial aconitase (ACO1) and evidence of a synergistic regulation of expression by glucose plus glutamate. Mol. Cell. Biol. 10: 3551-3561
  12. Goldie, H. and B. D. Sanwal. 1980. Genetic and physiological characterization of Escherichia coli mutants deficient in phosphoenolpyruvate carboxykinase activity. J. Bacteriol. 141: 1115-1121
  13. Guigo, R. 1997. Computational gene identification: An open problem. Comput. Chem. 21: 215-222
  14. Huynen, M. A., T. Dandekar, and P. Bork. 1999. Variation and evolution of citric-acid cycle: A genomic perspective. Trends Microbiol. 7(1): 281-291
  15. Latgé, J. P. 1999. Aspergillus fumigatus and aspergillosis. Clin. Microbiol. Rev. 12: 310-350
  16. Lombardo, A., K. Carine, and I. E. Scheffler. 1990. Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae. J. Biol. Chem. 265: 10419-10423
  17. Lorenz, M. C. and G. R. Fink. 2001. The glyoxylate cycle is required for fungal virulence. Nature 412: 83-86
  18. McAlister-Henn, L. and L. M. Thompson. 1987. Isolation and expression of the gene encoding yeast mitochondrial malate dehydrogenase. J. Bacteriol. 169: 5157-5166
  19. Mellado, E., G. Dubreucq, P. Mol, J. Sarfati, S. Paris, M. Diaquin, D. W. Holden, J. L. Rodriguez-Tudela, and J. P. Latgé. 2003. Cell wall biogenesis in a double chitin synthase mutant (chsG-/chsE-) of Aspergillus fumigatus. Fungal Genet. Biol. 38: 98-109 https://doi.org/10.1016/S1087-1845(02)00516-9
  20. Przybyla-Zawislak, B., R. A. Dennis, S. O. Zakharkin, and M. T. McCammon. 1998. Genes of succinyl-CoA ligase from Saccharomyces cerevisiae. Eur. J. Biochem. 248: 736- 743
  21. Przybyla-Zawislak, B., D. M. Gadde, K. Ducharme, and M. T. McCammon. 1999. Genetic and biochemical interactions involving tricarboxylic acid cycle (TCA) function using a collection of mutants defective in all TCA cycle genes. Genetics 152: 153-166
  22. Radford, A. and J. H. Parish. 1997. The genome and genes of Neurospora crassa. Fungal Genet. Biol. 21: 258-266
  23. Raper, K. B. and D. I. Fennell. 1965. Aspergillus fumigatus group. pp. 238-268. In Raper, K. B and D. I. Fennell (eds.), The genus Aspergillus. Wilkins & Wilkins, Baltimore, MD, U.S.A
  24. Repetto, B. and A. Tzagoloff. 1989. Structure and regulation of KGD1, the structure gene for the yeast $\alpha$-ketoglutarate dehydrogenase. Mol. Cell. Biol. 9: 2695-2705
  25. Repetto, B. and A. Tzagoloff. 1990. Structure and regulation of KGD2, the structure gene for yeast dihydrolipoyl transuccinylase. Mol. Cell. Biol. 10: 4221-4232
  26. Ross, J., G. A. Reid, and I. W. Dawes. 1988. The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae: Comparison between eukaryotic and prokaryotic sequences for related enzymes and identification of potential upstream control sites. J. Gen. Microbiol. 134: 1131-1139
  27. Salzberg, S. L., M. Pertea, A. L. Delcher, M. J. Gardner, and H. Tettelin. 1999. Interpolated Markov models for eukaryotic gene finding. Genomics 59: 24-31
  28. Suissa, M., K. Suda, and G. Schatz. 1984. Isolation of the nuclear yeast genes for citrate synthase and fifteen other mitochondrial proteins by a new screening method. EMBO J. 3: 1773-1781
  29. Wu, M. and A. Tzagoloff. 1987. Mitochondrial and cytoplasmic fumarases in Saccharomyces cerevisiae are encoded by a single nuclear gene FUM1. J. Biol. Chem. 262: 12275-12282