Gene disruption to evaluate the role of fungal candidate virulence genes

Current Opinion in Microbiology

Volumn 1, Issue 4, 1998, Pages 381-389

  Kwon Chung, K J ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AJELLOMYCES CAPSULATUS; CANDIDA ALBICANS; FILOBASIDIELLA NEOFORMANS; FUNGI;

CANDIDA; CRYPTOCOCCUS NEOFORMANS; FUNGAL GENE; GENE DELETION; GENETICS; MUTAGENESIS; PATHOGENICITY; REVIEW; VIRULENCE;

CANDIDA; CRYPTOCOCCUS NEOFORMANS; GENE DELETION; GENES, FUNGAL; MUTAGENESIS; VIRULENCE;

EID: 0032129784     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1369-5274(98)80053-2     Document Type: Article

References (59)

1. Kwon-Chung KJ, Polacheck I, Popkin TJ: Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. J Bacteriol 1982, 150:1414-1421.
2. Kwon-Chung KJ, Rhodes JC: Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans. Infect Immun 1986, 51:218-223.
3. Tsai H-F, Washburn RG, Chang YC, Kwon-Chung KJ: Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition. Mol Microbiol 1997, 26:175-183.
4. Petter R, Kwon-Chung KJ: Disruption of the SNF1 gene abolishes trehalose utilization in the pathogenic yeast Candida glabrata. Infect Immun 1996, 64:5269-5273.
5. Fonzi WI, Irwin MY: Isogenic strain construction and gene mapping in Candida albicans. Genetics 1993, 134:717-728.
6. Sanglard D, Tongi G, de Viragh PA, Monod M: Disruption of the gene encoding the secreted acid protease (ACP) in the yeast Candida tropicalis. FEMS Microbiol Lett 1992, 74:149-156.
7. Chang YC, Kwon-Chung KJ: Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol Cell Biol 1994, 14:4912-4919.
8. Rothstein R: One step gene disruption in yeast Methods Enzymol 1983, 101:202-211.
9. Woods JP, Goldman WE: In vivo generation of linear plasmids with addition of telomeric sequences by Histoplasma capsulatum. Mol Microbiol 1992, 6:3603-3610.
10. Edman JC, Kwon-Chung KJ: Isolation of the URA5 gene from Cryptococcus neoformans and their use in high-efficiency transformation. Mol Cell Biol 1990, 10:4538-4544.
11. Geber A, Hitchcok CA, Swartz EJ, Pullen FS, Marsden KE, Kwon-Chung KJ, Bennett JE: Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol-composition and antifungal susceptibility. Antimicrob Agents Chemother 1995, 39:2708-2717.
12. Perfect JR, Toffaletti DL, Rude TH: The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid. Infect Immun 1993, 61:4446-4451.
13. Odom A, Muir S, Lim E, Toffaletti DL, Perfect J, Heitman J: Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J 1997, 16:2576-2589. This is the first report showing that calcineurin A (a highly conserved, calcium regulated protein phosphatase) is essential for the viability of C. neoformans at 37°C.
14. Alspaugh JA, Perfect JR, Heitman J: Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP in C. neoformans. Genes Dev 1997, 11:3206-3217. This study shows that a heterotrimeric G protein's a subunit (GPA1) regulates not only mating but also virulence-associated traits such as capsule and melanin formation in C. neoformans. This study also shows that exogenous cAMP can restore the function of GPA1.
15. Lodge JK, Jackson-Machelski E, Toffaletti DL, Perfect JR, Gordon JI: Targeted gene replacement demonstrates that myristoyl-CoA:protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc Natl Acad Sci USA 1994, 91:12008-12012.
16. Chang YC, Penoyer LA, Kwon-Chung KJ: The second capsule gene of Cryptococcus neoformans, CAP64, is essential for virulence. Infect Immun 1996, 64:1977-1983.
17. Chang YC, Kwon-Chung KJ: Isolation of the third capsule associated gene, CAP60, required for virulence in Cryptococcus neoformans. Infect Immun 1998, 66:2230-2236. This paper characterizes the third capsule gene and shows that the gene product is localized in an association with the nuclear membrane in C. neoformans.
18. Salas SD, Bennett JE, Kwon-Chung KJ, Perfect JR: Effect of the laccase gene, CNLAC1, on virulence of Cryptococcus neoformans. J Exp Med 1996, 184:377-386.
19. Aramayo R, Timberlake WE: Sequence and molecular structure of the Aspergillus nidulans yA (laccase I) gene. Nucleic Acids Res 1990, 18:3415.
20. Collins PJ, Dobson AD: Regulation of laccase gene transcription. Appl Environ Microbiol 1997, 63:3444-3450.
21. Mody CH, Toews GB, Lipscomb MF: Cyclosporin A inhibits the growth of Cryptococcus neoformans in a murine model. Infect Immun 1988, 56:7-12.
22. Sabatini DM, Erdjument-Bromage H, Liu M, Tempst P, Snyder SH: RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994, 78:35-43.
23. Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, Wiederrecht G, Abraham RT: Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 1995, 270:815-822.
24. Wickes BL, Edman U, Edman JC: The Cryptococcus neoformans STE12α gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific. Mol Microbiol 1997, 26:951-960. This is the first study to report that the transcriptional activator STE12α is found only in the α mating type in C. neoformans and that the gene is responsible for monokaryotic fruiting. The study also supports the role of STE12α in the regulation of melanin formation in C. neoformans.
25. Lorenz MC, Heitman J: Yeast pseudohyphal growth is regulated by GPA2, a G protein α homolog. EMBO J 1997, 16:7008-7018.
26. Isshiki T, Mochizuki N, Maeda T, Yamamoto M: Characterization of a fission yeast gene, gpa2, that encodes a Ga subunit involved in the monitoring of nutrition. Genes Dev 1992, 6:2455-2462.
27. Chen B, Gao S, Choi GH, Nuss DL: Extensive alteration of fungal gene transcript accumulation and elevation of G-protein-regulated cAMP levels by a virulence-attenuating hypovirus. Proc Natl Acad Sci 1996, 93:7996-8000.
28. Gold S, Duncan G, Barrett K, Kronstad J: cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis. Genes Dev 1994, 8:2805-2816.
29. Thomas KR, Cappecchi MR: Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene. Nature 1986, 324:34-38.
30. Kwon-Chung KJ, Bennett JE: Distribution of α and a mating types of Cryptococcus neoformans among natural and clinical isolates. Am J Epidemiol 1978, 108:337-341.
31. Mansour SL, Thomas KR, Capecchi MR: Disruption of the protooncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 1988, 336:348-352.
32. Varma A, Edman JC, Kwon-Chung KJ: Molecular and genetic analysis of URA5 transformation system in Cryptococcus neoformans. Infect Immun 1992, 60:1101-1108.
33. Falkow S: Molecular Koch's postulates applied to microbial pathogenicity. Rev Infect Dis 1988, 10:S274-S276.
34. Odds FC: Candida species and virulence. ASM News 1994, 60:313-318.
35. Hube B, Monod M, Schofeld DA, Brown AJP, Gow NAR: Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol 1994, 14:87-99.
36. Cutler J: Putative virulence factors of Candida albicans. Annu Rev Microbiol 1991, 45:187-218.
37. Saporito-Irwin SM, Birse CE, Sypherd PS, Fonzi W: PHR1, a pH-regulated gene of Candida albicans, is required for morphogenesis. Mol Cell Biol 1995, 15:601-613.
38. Mühlschulegel FA, Fonzi WA: PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with inverted pattern of pH-dependent expression. Mol Cell Biol 1997, 17:5960-5967.
39. Lo H-J, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR: Nonfilamentous C. albicans mutants are avirulent Cell 1997, 90:939-94. This paper shows that two regulatory proteins encoded by the genes CPH1 and EFG1 are involved in filamentous growth in both C. albicans and S. cerevisiae (STE12 is the homolog of CPH1 and PHD1 is the homolog of EFG1). The double mutants of these genes are defective in filamentous growth and the homozygous double mutant cph1 egf11 of C. albicans is nearly avirulent for mice. This study shows the importance in fungal pathogenicity of the conserved genes encoding regulatory proteins, rather than the species-specific genes.
40. Gale CA, Bendel CM, Hauser M, Becker JM, Berman J, Hostetter MK: Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science 1998, 279:1355-1358. This study shows that the integrin of C. albicans encoded by INT1 enables S. cerevisiae to adhere to human epithelial cells. Int1p in C. albicans is involved in adhesion as well as filamentous growth, suggesting that there are multiple pathways which trigger yeast to hyphal morphologic switch.
41. Sanglard D, Hube B, Monod M, Odds F, Gow AR: A triple deletion of the secreted aspartyl proteinase genes SAP4, SAP5, and SAP6 of Candida albicans cause attenuated virulence. Infect Immun 1997, 65:3539-3546. This study shows that although a triple disruption of aspartyl proteinase genes in C. albicans does not affect the growth rate of C. albicans in complex media, it does affect fungal virulence in the murine model. Complementation studies will confirm this finding.
42. Hube B, Sanglard D, Odds F, Hess D, Monod M, Schafer W, Brown AJP, Gow AR: Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect Immun 1997, 65:3529-3538.
43. Alani E, Cao L, Kleckner N: A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics 1987, 116:541-545.
44. Watts HJ, Cheah FSH, Hube B, Sanglard D, Gow NAR: Altered adherence in strains of Candida albicans harbouring null mutations in secreted aspartic proteinase genes. FEMS Microbiol Lett 1998, 159:129-135.
45. Braun BR, Johnson AD: Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science 1997, 277:105-109. In this study, the TUP1 gene, which encodes a transcriptional repressor, was isolated from C. albicans. It was shown that the tup1/tup1 mutant grows exclusively as filaments regardless of environmental conditions. The experimental model suggest that TUP1 represses genes responsible for initiating filamentous growth and the repression is lifted under some conditions, such as the presence of serum in the environment. Virulence data were not presented but the authors indicated that the tup1/tup1 mutant was less infectious in mice than the wild type. The animal model used may not have been appropriate for such strains.
46. Liu H, Kohler J, Fink G: Suppression of hyphal formation by a mutation in the Candida albicans STE12 homolog. Science 1994, 266:1723-1726.
47. Stoldt VR, Sonneborn A, Leuker CE, Ernst JF: Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processess in fungi. EMBO J 1997, 16:1982-1991.
48. Gale C, Finkel D, Tao N, Meinke M, McClellan M, Olson J, Kendrick, K, Hostetter M: Cloning and expression of a gene encoding an integrin-like protein in Candida albicans. Proc Natl Acad Sci USA 1996, 93:357-361.
49. Petter R, Chang YC, Kwon-Chung KJ: A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for viability of Candida albicans. Infect Immun 1997, 65:4909-4917.
50. Jaton-Ogay K, Paris S, Huerre M, Quadroni M, Falchetto R, Tongli G, Latge JP, Monod M: Cloning and disruption of the gene encoding an extracellular metalloprotease of Aspergillus fumigatus. Mol Microbiol 1991, 14:917-928.
51. phox-/- mice: implications for fungal pathogenicity and host defense in chronic granulomatous disease. J Clin Invest 1998, 101:1843-1850. Contrary to the understanding that catalase is an important factor for microbial pathogenicity in patients with Chronic Granulomatous Disease (CGD), a rare genetic disorder, this study shows no significant pathogenic role of fungal catalases in CGD mice.
52. Aufauvre-Brown A, Mellado E, Gow NAR, Holden D: Aspergillus fumigatus chsE: A gene related to CHS3 of Saccharomyces cerevisiae and important for hyphal growth and conidiophore development but not pathogenicity. Fungal Genet Biol 1997, 21:141-152.
53. Holden DW, Tang CM, Smith JM: Molecular genetics of Aspergillus pathogenicity. Antonie van Leeuwenhoek 1994, 65:251-255.
54. Tsai H-F, Chang YC, Washburn RG, Wheeler MH, Kwon-Chung KJ: Developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial pigment and virulence. J Bacteriol 1998, 180:3031-3038. The authors demonstrated not only that the conidial pigment of Aspergillus fimigatus is synthesized via the dihydroxynaphthalene-melanin pathway, but also that conidial pigment plays a role in virulence of the fungus. Further analysis identified the developmentally regulated gene alb1, which encodes a putative polyketide synthase; its disruption results in albino conidia with altered surface morphology. This is the first report of a virulence gene of A. fumigatus.
55. Hogan LH, Josvai S, Klein BS: Genomic cloning, characterization, and functional analysis of the major surface adhesin WI-I on Blastomyces dermatitidis yeasts. J Biol Chem 1997, 270:30725-30732.
56. Yu JJ, Smithson SL, Thomas PW, Kirkland TN, Cole GT: Isolation and characterization of the urease gene (URE) from the pathogenic fungus Coccidioides immitis. Gene 1997, 198:387-391.
57. Yu JJ, Cole GT: Biolistic transformation of the human pathogenic fungus Coccidioides immitis. J Microbiol Methods 1998, 33:in press.
58. Hogan LH, Klein BS: Transforming DNA integrates at multiple sites in the dimorphic fungal pathogen Blastomyces dermatitidis. Gene 1997, 186:219-226.
59. Hamer JE, Holden DW: Linking approaches in the study of fungal pathogenesis: a commentary. Fungal Genet Biol 1997, 21:11-16. This minireview deals with the approaches that have been used to investigate fungal pathogenic mechanisms in both plant and animal pathogens. Similar involvements of specific signal transduction pathways in pathogenesis of fungi affecting both plants and animals are also discussed.