Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis

Eukaryotic Cell

Volumn 8, Issue 3, 2009, Pages 315-326

  Idnurm, Alexander ^a,b   Walton, Felicia J ^a,c   Floyd, Anna ^a   Reedy, Jennifer L ^a   Heitman, Joseph ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; VIRULENCE FACTOR;

ANIMAL; ARTICLE; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; ENZYMOLOGY; EVALUATION; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; METHODOLOGY; MICROBIOLOGY; MOUSE; PATHOGENICITY;

ADENOSINE TRIPHOSPHATASES; ANIMALS; CRYPTOCOCCOSIS; CRYPTOCOCCUS NEOFORMANS; HUMANS; MICE; MUTAGENESIS, INSERTIONAL; VIRULENCE FACTORS;

ANIMALIA; FILOBASIDIELLA NEOFORMANS; FUNGI; MAMMALIA; MURINAE; MUS;

EID: 61949322731     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00375-08     Document Type: Article

References (65)

1. Bahn, Y.-S., K. Kojima, G. M. Cox, and J. Heitman. 2005. Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol. Biol. Cell 16:2285-2300.
2. Bañuelos, M. A., and A. Rodríguez-Navarro. 1998. P-type ATPases mediate sodium and potassium effluxes in Schwanniomyces occidentalis. J. Biol. Chem. 273:1640-1646.
3. Bartlett, K. H., S. E. Kidd, and J. W. Kronstad. 2007. The emergence of Cryptococcus gattii in British Columbia and the Pacific Northwest. Curr. Fungal Infect. Rep. 1:108-115.
4. Benito, B., B. Garciadeblás, and A. Rodríguez- Navarro. 2002. Potassium- or sodium-efflux ATPase, a key enzyme in the evolution of fungi. Microbiology 148:933-941.
5. Betts, M. F., S. L. Tucker, N. Galadima, Y. Meng, G. Patel, L. Li, N. Donofrio, A. Floyd, S. Nolin, D. Brown, M. A. Mandel, T. K. Mitchell, J.-R. Xu, R. A. Dean, M. L. Farman, and M. J. Orbach. 2007. Development of a high throughput transformation system for insertional mutagenesis in Magnaporthe oryzae. Fungal Genet. Biol. 44:1035-1049.
6. Blaise, F., E. Rémy, M. Meyer, L. Zhou, J.-P. Narcy, J. Roux, M.-H. Balesdent, and T. Rouxel. 2007. A critical assessment of Agrobacterium tumefaciens-mediated transformation as a tool for pathogenicity gene discovery in the phytopathogenic fungus Leptosphaeria maculans. Fungal Genet. Biol. 44:123-138.
7. Brown, J. S., A. Aufauvre-Brown, J. Brown, J. M. Jennings, H. Arst, Jr., and D. W. Holden. 2000. Signature-tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity. Mol. Microbiol. 36:1371-1380.
8. Bundock, P., H. van Attikum, A. den Dulk-Ras, and P. J. J. Hooykaas. 2002. Insertional mutagenesis in yeasts using T-DNA from Agrobacterium tumefaciens. Yeast 19:529-536.
9. Casadevall, A., and J. Perfect. 1998. Cryptococcus neoformans. American Society for Microbiology Press, Washington, DC.
10. Chang, Y. C., and K. J. Kwon-Chung. 1994. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol. Cell. Biol. 14:4912-4919.
11. Choi, J., J. Park, J. Jeon, M.-H. Chi, J. Goh, S.-Y. Yoo, J. Park, K. Jung, H. Kim, S.-Y. Park, H.-S. Rho, S. Kim, B. R. Kim, S.-S. Han, S. Kang, and Y.-H. Lee. 2007. Genome-wide analysis of T-DNA integration into the chromosomes of Magnaporthe oryzae. Mol. Microbiol. 66:371-382.
12. Cormack, B. P., N. Ghori, and S. Falkow. 1999. An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells. Science 285:578-582.
13. Cox, G. M., J. Mukherjee, G. T. Cole, A. Casadevall, and J. R. Perfect. 2000. Urease as a virulence factor in experimental cryptococcosis. Infect. Immun. 68:443-448.
14. Dunn-Coleman, N., and H. Wang. 1998. Agrobacterium T-DNA: a silver bullet for filamentous fungi? Nat. Biotechnol. 16:817-818.
15. Erickson, T., L. Liu, A. Gueyikian, X. Zhu, J. Gibbons, and P. R. Williamson. 2001. Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1. Mol. Microbiol. 42:1121-1131.
16. 2+-ATPase, is involved in stress tolerance and virulence in Cryptococcus neoformans. Infect. Immun. 75:3394-3405.
17. Fuchs, B. B., and E. Mylonakis. 2006. Using non-mammalian hosts to study fungal virulence and host defense. Curr. Opin. Microbiol. 9:346-351.
18. 2+-ATPase in Schizosaccharomyces pombe. J. Biol. Chem. 265:18400-18407.
19. Goins, C. L., K. J. Gerik, and J. K. Lodge. 2006. Improvements to gene deletion in the fungal pathogen Cryptococcus neoformans: absence of Ku proteins increases homologous recombination, and co-transformation of independent DNA molecules allows rapid complementation of deletion phenotypes. Fungal Genet. Biol. 43:531-544.
20. Haro, R., B. Garciadeblas, and A. Rodríguez-Navarro. 1991. A novel P-type ATPase from yeast involved in sodium transport. FEBS Lett. 291:189-191.
21. Hensel, M., J. E. Shea, C. Gleeson, M. D. Jones, E. Dalton, and D. W. Holden. 1995. Simultaneous identification of bacterial virulence genes by negative selection. Science 269:400-403.
22. Idnurm, A., Y.-S. Bahn, K. Nielsen, X. Lin, J. A. Fraser, and J. Heitman. 2005. Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat. Rev. Microbiol. 3:753-764.
23. Idnurm, A., and J. Heitman. 2005. Light controls growth and development via a conserved pathway in the fungal kingdom. PLoS Biol. 3:615-626.
24. Idnurm, A., J. L. Reedy, J. C. Nussbaum, and J. Heitman. 2004. Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryot. Cell 3:420-429.
25. Ingavale, S. S., Y. C. Chang, H. Lee, C. M. McClelland, M. L. Leong, and K. J. Kwon-Chung. 2008. Importance of mitochondria in survival of Cryptococcus neoformans under low oxygen conditions and tolerance to cobalt chloride. PLoS Pathog. 4:e1000155.
26. Jeon, J., S.-Y. Park, M.-H. Chi, J. Choi, J. Park, H.-S. Rho, S. Kim, J. Goh, S. Yoo, J. Choi, J.-Y. Park, M. Yi, S. Yang, M.-J. Kwon, S.-S. Han, B. R. Kim, C. H. Khang, B. Park, S.-E. Lim, K. Jung, S. Kong, M. Karunakaran, H.-S. Oh, H. Kim, S. Kim, J. Park, S. Kang, W.-B. Choi, S. Kang, and Y.-H. Lee. 2007. Genome-wide functional analysis of pathogenicity genes in the rice blast fungus. Nat. Genet. 39:561-565.
27. Kimata, Y., and K. Kohno. 1994. Elongation factor 2 mutants deficient in diphthamide formation show temperature-sensitive cell growth. J. Biol. Chem. 269:13497-13501.
28. Kojima, K., Y.-S. Bahn, and J. Heitman. 2006. Calcineurin, Mpk1, and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans. Microbiology 152:591-604.
29. Kullas, A. L., S. J. Martin, and D. Davis. 2007. Adaptation to environmental pH: integrating the Rim101 and calcineurin signal transduction pathways. Mol. Microbiol. 66:858-871.
30. Lamb, T. M., and A. P. Mitchell. 2003. The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol. Cell. Biol. 23:677-686.
31. Li, G., Z. Zhou, G. Liu, F. Zheng, and C. He. 2007. Characterization of T-DNA insertion patterns in the genome of rice blast fungus Magnaporthe oryzae. Curr. Genet. 51:233-243.
32. Liu, O. W., C. D. Chun, E. D. Chow, C. Chen, H. D. Madhani, and S. M. Noble. 2008. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135:174-188.
33. Liu, S., G. T. Milne, J. G. Kuremsky, G. R. Fink, and S. H. Leppla. 2004. Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Mol. Cell. Biol. 24:9487-9497.
34. Loftus, B. J., E. Fung, P. Roncaglia, D. Rowley, P. Amedeo, D. Bruno, J. Vamathevan, M. Miranda, I. J. Anderson, J. A. Fraser, J. E. Allen, I. E. Bosdet, M. R. Brent, R. Chiu, T. L. Doering, M. J. Donlin, C. A. D'Souza, D. S. Fox, V. Grinberg, J. Fu, M. Fukushima, B. J. Haas, J. C. Huang, G. Janbon, S. J. M. Jones, H. L. Koo, M. I. Krzywinski, J. K. Kwon-Chung, K. B. Lengeler, R. Maiti, M. A. Marra, R. E. Marra, C. A. Mathewson, T. G. Mitchell, M. Pertea, F. R. Riggs, S. L. Salzberg, J. E. Schein, A. Shvartsbeyn, H. Shin, M. Shumway, C. A. Specht, B. B. Suh, A. Tenney, T. R. Utterback, B. L. Wickes, J. R. Wortman, N. H. Wye, J. W. Kronstad, J. K. Lodge, J. Heitman, R. W. Davis, C. M. Fraser, and R. W. Hyman. 2005. The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 307:1321-1324.
35. Majka, J., and P. M. J. Burgers. 2003. Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc. Natl. Acad. Sci. USA 100:2249-2254.
36. McClelland, C. M., Y. C. Chang, and K. J. Kwon-Chung. 2005. High frequency transformation of Cryptococcus neoformans and Cryptococcus gattii by Agrobacterium tumefaciens. Fungal Genet. Biol. 42:904-913.
37. Meng, Y., G. Patel, M. Heist, M. F. Betts, S. L. Tucker, N. Galadima, N. M. Donofrio, D. Brown, T. K. Mitchell, L. Li, J.-R. Xu, M. Orbach, M. Thon, R. A. Dean, and M. L. Farman. 2007. A systematic analysis of T-DNA insertion events in Magnaporthe oryzae. Fungal Genet. Biol. 44:1050-1064.
38. + gene encoding pyridoxal reductase of Schizosaccharomyces pombe. J. Biochem. 135:225-230.
39. Moyrand, F., T. Fontaine, and G. Janbon. 2007. Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol. Microbiol. 64:771-781.
40. Mylonakis, E., A. Casadevall, and F. M. Ausubel. 2007. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi. PLoS Pathog. 3:e101.
41. Mylonakis, E., A. Idnurm, R. Moreno, J. El Khoury, J. B. Rottman, F. M. Ausubel, J. Heitman, and S. B. Calderwood. 2004. Cryptococcus neoformans Kin1 protein kinase homologue, identified through a Caenorhabditis elegans screen, promotes virulence in mammals. Mol. Microbiol. 54:407-419.
42. Mylonakis, E., R. Moreno, J. B. El Khoury, A. Idnurm, J. Heitman, S. B. Calderwood, F. M. Ausubel, and A. Diener. 2005. Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect. Immun. 73:3842-3850.
43. Nacry, P., C. Camilleri, B. Courtial, M. Caboche, and D. Bouchez. 1998. Major chromosomal rearrangements induced by T-DNA transformation in Arabidopsis. Genetics 149:641-650.
44. Nelson, R. T., J. Hua, B. Pryor, and J. K. Lodge. 2001. Identification of virulence mutants of the fungal pathogen Cryptococcus neoformans using signature-tagged mutagenesis. Genetics 157:935-947.
45. Nielsen, K., G. M. Cox, A. P. Litvintseva, E. Mylonakis, S. D. Malliaris, D. K. Benjamin, Jr., S. S. Giles, T. G. Mitchell, A. Casadevall, J. R. Perfect, and J. Heitman. 2005. Cryptococcus neoformans α strains preferentially disseminate to the central nervous system during coinfection. Infect. Immun. 73:4922-4933.
46. Nielsen, K., G. M. Cox, P. Wang, D. L. Toffaletti, J. R. Perfect, and J. Heitman. 2003. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and α isolates. Infect. Immun. 71:4831-4841.
47. Niggli, V., and E. Sigel. 2008. Anticipating antiport in P-type ATPases. Trends Biochem. Sci. 33:156-160.
48. Odom, A., S. Muir, E. Lim, D. L. Toffaletti, J. Perfect, and J. Heitman. 1997. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 16:2576-2589.
49. Peñalva, M. A., J. Tilburn, E. Bignell, and H. N. Arst, Jr. 2008. Ambient pH gene regulation in fungi: making connections. Trends Microbiol. 16:291-300.
50. Pitkin, J. W., D. G. Panaccione, and J. D. Walton. 1996. A putative cyclic peptide efflux pump encoded by the TOXA gene of the plant-pathogenic fungus Cochliobolus carbonum. Microbiology 142:1557-1565.
51. +-ATPase ENA1 gene to alkaline stress involves three main signaling pathways. J. Biol. Chem. 281:36632-36642.
52. Ruiz, A., and J. Ariño. 2007. Function and regulation of the Saccharomyces cerevisiae ENA sodium ATPase system. Eukaryot. Cell 6:2175-2183.
53. Serrano, R., A. Ruiz, D. Bernal, J. R. Chambers, and J. Ariño. 2002. The transcriptional response to alkaline pH in Saccharomyces cerevisiae: evidence for calcium-mediated signalling. Mol. Microbiol. 46:1319-1333.
54. Shinohara, M., K. Sakai, T. Ogawa, and A. Shinohara. 2003. The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast. Genetics 164:855-856.
55. Takao, M., R. Yonemasu, K. Yamamoto, and A. Yasui. 1996. Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog. Nucleic Acids Res. 24:1267-1271.
56. Tang, C. M., J. M. Smith, H. N. Arst, Jr., and D. W. Holden. 1994. Virulence studies of Aspergillus nidulans mutants requiring lysine or p-aminobenzoic acid in invasive pulmonary aspergillosis. Infect. Immun. 62:5255-5260.
57. Tang, R. J., J. Breger, A. Idnurm, K. J. Gerik, J. K. Lodge, J. Heitman, S. B. Calderwood, and E. Mylonakis. 2005. Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach. Infect. Immun. 73:8219-8225.
58. Vartivarian, S. E., E. J. Anaissie, R. E. Cowart, H. A. Sprigg, M. J. Tingler, and E. S. Jacobson. 1993. Regulation of cryptococcal capsular polysaccharide by iron. J. Infect. Dis. 167:186-190.
59. Walton, F. J., J. Heitman, and A. Idnurm. 2006. Conserved elements of the RAM signaling pathway establish cell polarity in the basidiomycete Cryptococcus neoformans in a divergent fashion from other fungi. Mol. Biol. Cell 17:3768-3780.
60. Walton, F. J., A. Idnurm, and J. Heitman. 2005. Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans. Mol. Microbiol. 57:1381-1396.
61. + pump in the yeast plasma membrane. EMBO J. 14:3870-3882.
62. Williamson, P. R. 1994. Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase. J. Bacteriol. 176:656-664.
63. Yajima, H., M. Takao, S. Yasuhira, J. H. Zhao, C. Ishii, H. Inoue, and A. Yasui. 1995. A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light. EMBO J. 14:2393-2399.
64. Yeh, Y.-L., Y.-S. Lin, B.-J. Su, and W.-C. Shen. 2009. A screening for suppressor mutants reveals components involved in the blue light-inhibited sexual filamentation in Cryptococcus neoformans. Fungal Genet. Biol. 46:42-54.
65. Zhu, X., and P. R. Williamson. 2003. A CLC-type chloride channel gene is required for laccase activity and virulence in Cryptococcus neoformans. Mol. Microbiol. 50:1271-1282.