Signaling Pathways in the Dimorphic Human Fungal Pathogen Penicillium marneffei

Alex Andrianopoulos; Sophie Zuber

doi:10.1128/9781555815776.ch30

Chapter 30 : Signaling Pathways in the Dimorphic Human Fungal Pathogen Penicillium marneffei

Authors: Alex Andrianopoulos¹, Sophie Zuber²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Department of Genetics, University of Melbourne, Victoria 3010, Australia; 2: Quality and Safety Assurance Department, Nestle Research Center, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland

Content Type: Monograph

Publication Year: 2006

Category: Fungi and Fungal Pathogenesis

Book DOI: 10.1128/9781555815776

Chapter DOI: 10.1128/9781555815776.ch30

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Signaling Pathways in the Dimorphic Human Fungal Pathogen Penicillium marneffei, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap30-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap30-2.gif

Abstract:

This chapter focuses on the heterotrimeric G proteins and their role in growth and morphogenesis in the thermally dimorphic human pathogen Penicillium marneffei. Signaling is terminated when the intrinsic GTPase activity of the α subunit leads to the hydrolysis of GTP to GDP, thus leading to the reassociation of the α subunit and the βγ complex. There are three a subunits encoding genes identified in P. marneffei: gasA, gasB, and gasC. The gasA and gasC genes play distinct roles in P. marneffei morphogenesis yet show some overlap. Two major differences may explain this difference in regulation in P. marneffei compared to Saccharomyces cerevisiae and Ustilago maydis. First, the latter organisms are both predominantly yeasts that undergo a yeast-to-hypha transition while P. marneffei is predominantly hyphal and switches between a hyphal and yeast form. Second, the inducing signal(s) for dimorphic switching for the latter organisms is chemical in nature while the signal for P. marneffei is temperature, a physical signal. A growing number of genes encoding α subunits have been cloned from various fungal species, and their biological functions have been investigated. These studies have demonstrated the importance and the complexity of G protein signaling in the regulation of key processes of fungal life cycles, such as dimorphic switching, mating, asexual development, and pathogenicity.

Citation: Andrianopoulos A, Zuber S. 2006. Signaling Pathways in the Dimorphic Human Fungal Pathogen Penicillium marneffei, p 441-454. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch30

Key Concept Ranking

Protein G: 0.77581
Fungal Proteins: 0.6599597
Signal Transduction: 0.6020747
Signalling Pathway: 0.59331745

0.77581

Highlighted Text: Show | Hide

Full text loading...

Figures

Signaling Pathways in the Dimorphic Human Fungal Pathogen Penicillium marneffei

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815776.ch30-1,webId=/content/author/10.1128/9781555815776.ch30-1,properties={foaf_givenname=Alex, foaf_name=Alex Andrianopoulos, foaf_surname=Andrianopoulos, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815776.ch30-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815776.ch30-2,webId=/content/author/10.1128/9781555815776.ch30-2,properties={foaf_givenname=Sophie, foaf_name=Sophie Zuber, foaf_surname=Zuber, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815776.ch30-aff2]]}]]

/content/10.1128/9781555815776.ch30.ch30fig01

Figure 1.

P. marneffei life cycle. A diagram of the P. marneffei life cycle, showing the various vegetative growth and developmental stages, is presented. The solid circles represent nuclei in cells. The filamentous phase exhibited at 25°C is shown above the dashed line and is characterized by hyphal growth and the asexual development program which produces conidia. The yeast phase expressed at 37°C is shown below the dashed line and is characterized by the arthroconidiation program, yeast growth, and division by fission. The dimorphic switch which links the yeast and hyphal growth phases in response to temperature is shown. (From reference 2 with permission.)

10.1128/9781555815776/f0442-01_thmb.gif

10.1128/9781555815776/f0442-01.gif

Figure 1.

/content/10.1128/9781555815776.ch30.ch30fig02

Figure 2

Heterotrimeric G protein signaling. Heterotrimeric G proteins are trimers whose function depends on the ability to dissociate into an α monomer and a βγ dimer. G proteins are generally coupled to 7-TM receptors. When GDP is bound, the α subunit associates with the βγ subunit to form an inactive complex that binds to the receptor. On binding of the signal to the receptor, the α subunit becomes activated and exchanges GDP for GTP, thus dissociating from the receptor and the β complex. Both the α and βγ subunits can trigger downstream signaling pathways. RGS proteins accelerate the GTP hydrolysis rate of the Gα subunit, thus driving the GTP-bound α subunit back to the inactive GDP-bound form.

10.1128/9781555815776/f0443-01_thmb.gif

10.1128/9781555815776/f0443-01.gif

Figure 2

/content/10.1128/9781555815776.ch30.ch30fig03

Figure 3

Signaling by the gasA-encoded α subunit. GasA signaling at 25°C is likely to involve both a cAMP-PKA pathway and a MAPK pathway in the negative regulation of asexual development and the expression of the core regulatory factors BrlA and AbaA. GasA also plays a minor positive role in the regulation of secondary metabolic pathways. However, it has no apparent role during yeast cell morphogenesis at 37°C. The signal/ligand for this process is not defined. The degree of regulation of each process is indicated by the thickness of the line.

10.1128/9781555815776/f0445-01_thmb.gif

10.1128/9781555815776/f0445-01.gif

Figure 3

/content/10.1128/9781555815776.ch30.ch30fig04

Figure 4

Toxicological studies of GasA signaling. The predicted signaling pathway through GasA to the cAMP-PKA pathway, based on genetic and physiological studies using chemical inhibitors and analogues as well as known pathways in related fungi, is shown. Adenylate cyclase (AC), phosphodiesterase (PDE), and PKA with its catalytic (C) and regulatory (R) subunits are illustrated, as is the action of H-89, theophylline, and dbcAMP on the cAMP-PKA pathway. The effect of these toxicological agents on growth and development for the wild type (GasA) and the strains carrying either a gasA dominant activating (GasAACT), dominant negative (GasANEG), or deletion (∆GasA) allele is presented. The studies support the involvement of a cAMP-PKA pathway in GasA signaling.

10.1128/9781555815776/f0446-01_thmb.gif

10.1128/9781555815776/f0446-01.gif

Figure 4

/content/10.1128/9781555815776.ch30.ch30fig05

Figure 5

Control of conidial germination. Conidial germination in P. marneffei is controlled by the action of the α-subunit-encoding gasC, the Ras GTPase-encoding rasA, and the small Rho-type (CDC42) GTPase-encoding cflA genes. Dominant activated gasCACT or dominant activated cflAACT alleles result in precocious germination under inducing conditions (i.e., presence of a carbon source). Conidial germination is delayed in a ∆gasC strain or in strains carrying the dominant negative cflANEG allele or dominant negative or dominant activated rasAACT /rasANEG alleles. The rasA gene is upstream of cflA based on genetic interaction studies.

10.1128/9781555815776/f0448-01_thmb.gif

10.1128/9781555815776/f0448-01.gif

Figure 5

/content/10.1128/9781555815776.ch30.ch30fig06

Figure 6

Proposed model for signal transduction pathways regulating germination, asexual development, and secondary metabolism in P. marneffei. The α subunit GasC plays a major role in the regulation of germination. GasC also regulates the production of secondary metabolites and, to a lesser extent, asexual development. The action of the subunit in GasC signaling is unclear, and it is proposed that GasC acts through the cAMP-PKA pathway. The signals and receptors linked to this G protein are unknown. The degree of regulation of each process is indicated by the thickness of the line.

10.1128/9781555815776/f0449-01_thmb.gif

10.1128/9781555815776/f0449-01.gif

Figure 6

/content/10.1128/9781555815776.ch30.ch30fig07

Figure 7

Proposed model for G protein signaling in P. marneffei. The α subunit GasA signals via the cAMP-PKA pathway and a MAPK pathway to regulate asexual development and, to a lesser extent, secondary metabolism. GasC plays a major role in the regulation of germination. GasC also regulates secondary metabolites and, to a lesser extent, asexual development and is proposed to signal through the cAMP-PKA pathway. The overlap between GasA and GasC function may reflect the fact that they may share a subunit. The action of the α subunit GasB is unknown. The degree of regulation of each process is indicated by the thickness of the line.

10.1128/9781555815776/f0450-01_thmb.gif

10.1128/9781555815776/f0450-01.gif

Figure 7

References

/content/book/10.1128/9781555815776.ch30

1. Alexopoulos, C. J.,, C. W. Mims, and, M. Blackwell. 1996. Introductory Mycology. John Wiley & Sons, Inc., New York, N.Y.

2. Andrianopoulos, A. 2002. Control of morphogenesis in the human fungal pathogen Penicillium marneffei. Int. J. Med. Microbiol. 292: 331– 347.

3. Baasiri, R. A.,, X. Lu,, P. S. Rowley,, G. E. Turner, and, K. A. Borkovich. 1997. Overlapping functions for two G protein α subunits in Neurospora crassa. Genetics 147: 137– 145.

4. Bardwell, L. 2005. A walk-through of the yeast mating pheromone response pathway. Peptides 26: 339– 350.

5. Böhm, S. K.,, E. F. Grady, and, N. W. Bunnett. 1997. Regulatory mechanisms that modulate signalling by G-protein-coupled receptors. Biochem. J. 322: 1– 18.

6. Bölker, M. 1998. Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis. Fungal Genet. Biol. 25: 143– 156.

7. Borneman, A. R.,, M. J. Hynes, and, A. Andrianopoulos. 2000. The abaA homologue of Penicillium marneffei participates in two developmental programmes: conidiation and dimorphic growth. Mol. Microbiol. 38: 1034– 1047.

8. Borneman, A. R.,, M. J. Hynes, and, A. Andrianopoulos. 2001. An STE12 homolog from the asexual, dimorphic fungus Penicillium marneffei complements the defect in sexual development of an Aspergillus nidulans steA mutant. Genetics 157: 1003– 1014.

9. Bourne, H. R. 1997. How receptors talk to trimeric G proteins. Curr. Opin. Cell Biol. 9: 134– 142.

10. Boyce, K. J.,, M. J. Hynes, and, A. Andrianopoulos. 2001. The CDC42 homolog of the dimorphic fungus Penicillium marneffei is required for correct cell polarization during growth but not development. J. Bacteriol. 183: 3447– 3457.

11. Boyce, K. J.,, M. J. Hynes, and, A. Andrianopoulos. 2005. The Ras and Rho GTPases genetically interact to coordinately regulate cell polarity during development in Penicillium marneffei. Mol. Microbiol. 55: 1487– 1501.

12. Casey, P. J. 1994. Lipid modifications of G proteins. Curr. Opin. Cell Biol. 6: 219– 225.

13. Chan, Y., and, T. C. Chow. 1990. Ultrastructural observations on Penicillium marneffei in natural human infection. Ultrastruct. Pathol. 14: 439– 452.

14. Chang, M. H.,, K. S. Chae,, D. M. Han, and, K. Y. Jahng. 2004. The GanB Gα-protein negatively regulates a sexual sporulation and plays a positive role in conidial germination in Aspergillus nidulans. Genetics 167: 1305– 1315.

15. Choi, G. H.,, B. Chen, and, D. L. Nuss. 1995. Virus-mediated or transgenic suppression of a G-protein α subunit and attenuation of fungal virulence. Proc. Natl. Acad. Sci. USA 92: 305– 309.

16. Choi, W., and, R. A. Dean. 1997. The adenylate cyclase gene mac1 of Magnaporthe grisea controls appressorium formation and other aspects of growth and development. Plant Cell 9: 1973– 1983.

17. Clapham, D. E., and, E. J. Neer. 1997. G protein subunits. Annu. Rev. Pharmacol. Toxicol. 37: 167– 203.

18. Cooper, C. R. J. 1998. From bamboo rats to humans: the odyssey of Penicillium marneffei. ASM News 64: 390– 397.

19. d’Enfert, C. 1997. Fungal spore germination: insights from the molecular genetics of Aspergillus nidulans and Neurospora crassa. Fungal Genet. Biol. 21: 163– 172.

20. d’Enfert, C., and, T. Fontaine. 1997. Molecular characterization of the Aspergillus nidulans treA gene encoding an acid trehalase required for growth on trehalose. Mol. Microbiol. 24: 203– 216.

21. Deng, Z. L., and, D. H. Conner. 1985. Progressive disseminated penicilliosis caused by Penicillium marneffei: report of eight cases and differentiation of the causative organism from Histoplasma capsulatum. Am. J. Clin. Pathol. 84: 323– 327.

22. Eriksson, S.,, R. Hurme, and, M. Rhen. 2002. Low-temperature sensors in bacteria. Philos. Trans. R. Soc. Lond. Ser. B 357: 887– 893.

23. Fang, E. G., and, R. A. Dean. 2000. Site-directed mutagenesis of the magB gene affects growth and development in Magnaporthe grisea. Mol. Plant-Microbe Interact. 13: 1214– 1227.

24. Fillinger, S.,, M. K. Chaveroche,, K. Shimizu,, N. Keller, and, C. d’Enfert. 2002. cAMP and RAS signalling independently control spore germination in the filamentous fungus Aspergillus nidulans. Mol. Microbiol. 44: 1001– 1016.

25. Forsberg, H., and, P. O. Ljungdahl. 2001. Sensors of extra-cellular nutrients in Saccharomyces cerevisiae. Curr. Genet. 40: 91– 109.

26. Garrison, R. G., and, K. S. Boyd. 1973. Dimorphism of P. marneffei as observed by electron microscopy. Can. J. Microbiol. 19: 1305– 1309.

27. Gilman, A. G. 1987. G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56: 615– 649.

28. Hamm, H. E. 1998. The many faces of G protein signaling. J. Biol. Chem. 273: 669– 672.

29. Hampsey, M. 1997. A review of phenotypes in Saccharomyces cerevisiae. Yeast 13: 1099– 1133.

30. Harashima, T., and, J. Heitman. 2002. The Gα protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gβ subunits. Mol. Cell 10: 163– 173.

31. Hatanaka, M., and, C. Shimoda. 2001. The cyclic AMP/PKA signal pathway is required for initiation of spore germination in Schizosaccharomyces pombe. Yeast 18: 207– 217.

32. Herman, P. K., and, J. Rine. 1997. Yeast spore germination: a requirement for Ras protein activity during reentry into the cell cycle. EMBO J. 16: 6171– 6181.

33. Hicks, J. K.,, J. -H. Yu,, N. P. Keller, and, T. H. Adams. 1997. Aspergillus sporulation and mycotoxin production both require inactivation of the FadA Gα protein-dependent signaling pathway. EMBO J. 16: 4916– 4923.

34. Ivey, F. D.,, P. N. Hodge,, G. E. Turner, and, K. A. Borkovich. 1996. The Gαi homologue gna-1 controls multiple differentiation pathways in Neurospora crassa. Mol. Biol. Cell 7: 1283– 1297.

35. Ivey, F. D.,, Q. Yang, and, K. A. Borkovich. 1999. Positive regulation of adenylyl cyclase activity by a Gαi homolog in Neurospora crassa. Fungal Genet. Biol. 26: 48– 61.

36. Kays, A. M.,, P. S. Rowley,, R. A. Baasiri, and, K. A. Borkovich. 2000. Regulation of conidiation and adenylyl cyclase levels by the Gα protein GNA-3 in Neurospora crassa. Mol. Cell. Biol. 20: 7693– 7705.

37. Kölle, M. R. 1997. A new family of G-protein regulators —the RGS proteins. Curr. Opin. Cell Biol. 9: 143– 147.

38. Kübler, E.,, H. U. Mosch,, S. Rupp, and, M. P. Lisanti. 1997. Gpa2p, a G-protein α-subunit, regulates growth and pseudohyphal development in Saccaromyces cerevisiae via a cAMP-dependent mechanism. J. Biol. Chem. 272: 20321– 20323.

39. Kwon-Chung, K. J., and, J. E. Bennett. 1992. Medical Mycology. Lea & Febiger, Philadelphia, Pa.

40. Lafon, A.,, J. A. Seo,, K. H. Han,, J. H. Yu, and, C. d’Enfert. 2005. The heterotrimeric G-protein GanB(α)-SfaD(β)GpgA(γ) is a carbon source sensor involved in early cAMP-dependent germination in Aspergillus nidulans. Genetics 171: 71– 80.

41. Liebmann B.,, M. Muller,, A. Braun, and, A. A. Brakhage. 2004. The cyclic AMP-dependent protein kinase a network regulates development and virulence in Aspergillus fumigatus. Infect. Immun. 72: 5193– 5203.

42. Liu, S. H., and, R. A. Dean. 1997. G protein α-subunit genes control growth, development and pathogenicity of Magnaporthe grisea. Mol. Plant-Microbe Interact. 10: 1075– 1086.

43. Logothetis, D. E.,, Y. Kurachi,, J. Galper,, E. J. Neer, and, D. E. Clapman. 1987. The subunits of GTP-binding proteins activate the muscarinic K + channel in heart. Nature 325: 321– 326.

44. Lorenz, M. C., and, J. Heitman. 1997. Yeast pseudohyphal growth is regulated by Gpa2, a G protein α homolog. EMBO J. 16: 7008– 7018.

45. Loros, J. 2005. A kinase for light and time. Mol. Microbiol. 56: 299– 302.

46. Loubradou, G.,, J. Begueret, and, B. Turcq. 1999. MOD-D, a Gα subunit of the fungus Podospora anserina, is involved in both regulation of development and vegetative incompatibility. Genetics 152: 519– 528.

47. Martin, H.,, J. M. Rodriguez-Pachon,, C. Ruiz,, C. Nombela, and, M. Molina. 2000. Regulatory mechanisms for modulation of signaling through the cell integrity Slt2-mediated pathway in Saccharomyces cerevisiae. J. Biol. Chem. 275: 1511– 1519.

48. Neer, E. J. 1995. Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80: 249– 257.

49. Neves, S. R.,, P. T. Ram, and, R. Iyengar. 2002. G protein pathways. Science 296: 1636– 1639.

50. Obara, T.,, M. Nakafuku,, M. Yamamoto, and, Y. Kaziro. 1991. Isolation and characterization of a gene encoding a G-protein α subunit from Schizosaccharomyces pombe: involvement in mating and sporulation pathways. Proc. Natl. Acad. Sci. USA 88: 5877– 5881.

51. Osherov, N., and, G. May. 2000. Conidial germination in Aspergillus nidulans requires RAS signaling and protein synthesis. Genetics 155: 647– 656.

52. Osherov, N., and, G. S. May. 2001. The molecular mechanisms of conidial germination. FEMS Microbiol. Lett. 199: 153– 160.

53. Osherov, N.,, J. Mathew,, A. Romans, and, G. S. May. 2002. Identification of conidial-enriched transcripts in Aspergillus nidulans using suppression subtractive hybridization. Fungal Genet. Biol. 37: 197– 204.

54. Parsons, W. J.,, V. Ramkumar, and, G. L. Stiles. 1988. Isobutylmethylxanthine stimulates adenylate cyclase by blocking the inhibitory regulatory protein, Gi. Mol. Pharmacol. 34: 37– 41.

55. Pitcher, J. A.,, N. J. Freedman, and, R. J. Lefkowitz. 1998. G protein-coupled receptor kinases. Annu. Rev. Biochem. 67: 653– 692.

56. Pitt, J. I. 1979. The Genus Penicillium and Its Teleomorphic States Eupenicillium and Talaromyces. Academic Press, Inc., New York, N.Y.

57. Regenfelder, E.,, T. Spellig,, A. Hartmann,, S. Lauenstein,, M. Bölker, and, R. Kahmann. 1997. G-proteins in Ustilago maydis: transmission of multiple signals? EMBO J. 16: 1934– 1942.

58. Rens-Domiano, S., and, H. E. Hamm. 1995. Structural and functional relationships of heterotrimeric G-proteins. FASEB J. 9: 1059– 1066.

59. Rosen, S.,, J. H. Yu, and, T. H. Adams. 1999. The Aspergillus nidulans sfaD gene encodes a G protein β subunit that is required for normal growth and repression of sporulation. EMBO J. 18: 5592– 5600.

60. Segretain, G. 1959. Penicillium marneffei n. sp., agent d’une mycose du système réticuloendothélial. Mycopathol. Mycol. Appl. 11: 327– 353.

61. Seo, J. A.,, K. H. Han, and, J. H. Yu. 2005. Multiple roles of a heterotrimeric G protein γ subunit in governing growth and development of Aspergillus nidulans. Genetics 171: 81– 89.

62. Shimizu, K., and, N. P. Keller. 2001. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics 157: 591– 600.

63. Som, T., and, V. S. Kolaparthi. 1994. Developmental decisions in Aspergillus nidulans are modulated by Ras activity. Mol. Cell. Biol. 14: 5333– 5348.

64. Sirisanthana, T., and, K. Supparatpinyo. 1998. Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients. Int. J. Infect. Dis. 3: 48– 53.

65. Sirisanthana, T.,, K. Supparatpinyo,, J. Perriens, and, K. E. Nelson. 1998. Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 26: 1107– 1110.

66. Supparatpinyo, K.,, S. Chiewchanvit,, P. Hirunsri,, C. Uthammachai,, K. E. Nelson, and, T. Sirisanthana. 1992. Penicillium marneffei infection in patients infected with human immunodeficiency virus. Clin. Infect. Dis. 14: 871– 874.

67. Supparatpinyo, K.,, K. E. Nelson,, W. G. Merz,, B. J. Breslin,, C. R. Cooper,, C. Kamwan, and, T. Sirisanthana. 1993. Response to antifungal therapy by human immunodeficiency virus-infected patients with disseminated Penicillium marneffei infections and in vitro susceptibilities of isolates from clinical specimens. Antimicrob. Agents Chemother. 37: 2407– 2411.

68. Supparatpinyo, K.,, C. Khamwan,, V. Baosoung,, K. E. Nelson, and, T. Sirisanthana. 1994. Disseminated Penicillium marneffei infection in Southeast Asia. Lancet 344: 110– 113.

69. Turner, G. E., and, K. A. Borkovich. 1993. Identification of a G protein α subunit from Neurospora crassa that is a member of the Gi family. J. Biol. Chem. 268: 14805– 14811.

70. Vossler, J. 2001. Penicillium marneffei: an emerging fungal pathogen. Clin. Microbiol. News. 23: 25– 29.

71. Whiteway, M.,, L. Hougan,, D. Dignard,, D. Y. Thomas,, L. Bell,, G. C. Saari,, F. J. Grant,, P. O’Hara, and, V. L. MacKay. 1989. The STE4 and STE18 genes of yeast encode potential β and γ subunits of the mating factor receptor-coupled G protein. Cell 56: 467– 477.

72. Wong, S. S.,, H. Siau, and, K. Y. Yuen. 1999. Penicilliosis marneffei —West meets East. J. Med. Microbiol. 48: 973– 975.

73. Yang, Q., and, K. A. Borkovich. 1999. Mutational activation of a Gαi causes uncontrolled proliferation of aerial hyphae and increased sensitivity to heat and oxidative stress in Neurospora crassa. Genetics 151: 107– 117.

74. Yu, J. H.,, R. A. Butchko,, M. Fernandes,, N. P. Keller,, T. J. Leonard, and, T. H. Adams. 1996. Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr. Genet. 29: 549– 555.

75. Yu, J. H.,, J. Wieser, and, T. H. Adams. 1996. The Aspergillus FlbA RGS domain protein antagonizes G-protein signalling to block proliferation and allow development. EMBO J. 15: 5184– 5190.

76. Zuber, S.,, M. J. Hynes, and, A. Andrianopoulos. 2002. G-protein signaling mediates asexual development at 25°C but has no effect on yeast-like growth at 37°C in the dimorphic fungus Penicillium marneffei. Eukaryot. Cell 1: 440– 447.

77. Zuber, S.,, M. J. Hynes, and, A. Andrianopoulos. 2003. The G-protein α-subunit GasC plays a major role in germination in the dimorphic fungus Penicillium marneffei. Genetics 164: 487– 499.

78. Zuber, S. 2003. Regulatory mechanisms controlling development in the dimorphic fungus Penicillium marneffei. PhD thesis. University of Melbourne, Melbourne, Australia.