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Chapter 23 : Molecular Determinants of Pathogenesis

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Molecular Determinants of Pathogenesis, Page 1 of 2

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Abstract:

This chapter focuses on the pathogenic biology of , including a selection of both mechanisms and specific components; the latter all involve products secreted extracellularly and/or found on the cell surface. Once inhaled, conidia could give rise to yeasts prior to entry of the yeasts into host cells or conidia could be phagocytosed and then undergo the dimorphic transition inside host cells. Two yeast-specific genes, CBP1 and YPS3, are discussed individually. Testing of null mutant and complemented yeast strains confirmed the linkage of the EGTA resistance phenotype with functional CBP1 gene expression rather than with the yeast morphotype. This result raises the possibility that the calcium-binding protein plays a role in calcium acquisition akin to the function of siderophores in iron acquisition. Bad1 is an adhesin that mediates yeast binding to host cell CR3 and CD14; it is an immunosuppressive molecule that represses host tumor necrosis factor alpha production by both transforming growth factor β-dependent and -independent mechanisms, and it is an essential virulence determinant for animal infection. The fungal surface adhesin responsible for binding host β integrin receptors is the heat shock protein HSP60, which is discussed in more detail. Secretion of siderophores was first reported for over 20 years ago. Importantly, rough variants are relatively more virulent in animal and macrophage infection models than are smooth variants of the same strain. Conversely, several genes with important and interesting characteristics have been studied, but generally the function of these genes has not been entirely elucidated.

Citation: Woods J. 2006. Molecular Determinants of Pathogenesis, p 321-331. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch23

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Tumor Necrosis Factor alpha
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Restriction Fragment Length Polymorphism
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Figures

Image of Figure 1.
Figure 1.

Comparison of and genetic loci. Symbols: hatched bar, promoter region with conserved regulatory sequence motifs; solid bar, region encoding N-terminal hydrophobic signal sequence domain; white bar, region encoding tandem invasin-like repeat domains; cross-hatched bar, region encoding the C-terminal EGF-like domain.

Citation: Woods J. 2006. Molecular Determinants of Pathogenesis, p 321-331. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch23
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Image of Figure 2.
Figure 2.

iron acquisition mechanisms.

Citation: Woods J. 2006. Molecular Determinants of Pathogenesis, p 321-331. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch23
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References

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1. Abidi, F. E.,, H. Roh, and, E. J. Keath. 1998. Identification and characterization of a phase-specific, nuclear DNA binding protein from the dimorphic pathogenic fungus Histoplasma capsulatum. Infect. Immun. 66:38673873.
2. Appella, E.,, I. T. Weber, and, F. Blasi. 1988. Structure and function of epidermal growth factor-like regions in proteins. FEBS Lett. 231:14.
3. Batanghari, J. W.,, G. S. Deepe, Jr.,, E. D. Cera, and, W. E. Goldman. 1998. Histoplasma acquisition of calcium and expression of CBP1 during intracellular parasitism. Mol. Microbiol. 27:531539.
4. Batanghari, J. W., and, W. E. Goldman. 1997. Calcium dependence and binding in cultures of Histoplasma capsulatum. Infect. Immun. 65:52575261.
5. Bawdon, R. E.,, R. G. Garrison, and, L. R. Fina. 1972. Deoxyribonucleic acid base composition of the yeastlike and mycelial phases of Histoplasma capsulatum and Blastomyces dermatitidis. J. Bacteriol. 111:593596.
6. Bohse, M. L, and, J. P. Woods. 2005. Surface localization of the Yps3p protein of Histoplasma capsulatum. Eukaryot. Cell 4:685693.
7. Bowman, B. H.,, J. W. Taylor, and, T. J. White. 1992. Molecular evolution of the fungi: human pathogens. Mol. Biol. Evol. 9:893904.
8. Brandhorst, T. T., and, B. S. Klein. 2000. Cell wall biogenesis of Blastomyces dermatitidis. J. Biol. Chem. 275:79257934.
9. Brandhorst, T. T.,, M. Wuthrich,, B. Finkel-Jimenez, and, B. Klein. 2003. A C-terminal EGF-like domain governs BAD1 localization to the yeast surface and fungal adherence to phagocytes, but is dispensable in immune modulation and pathogenicity of Blastomyces dermatitidis. Mol. Microbiol. 48:5365.
10. Brandhorst, T. T.,, M. Wüthrich,, T. Warner, and, B. Klein. 1999. Targeted gene disruption reveals an adhesin indispensable for pathogenicity of Blastomyces dermatitidis. J. Exp. Med. 189:12071216.
11. Bullock, W. E., and, S. D. Wright. 1987. Role of the adherence-promoting receptors, CR3, LFA-1, and p150,95, in binding of Histoplasma capsulatum by human macrophages. J. Exp. Med. 165:195210.
12. Burt, W. R. 1982. Identification of coprogen B and its breakdown products from Histoplasma capsulatum. Infect. Immun. 35:990996.
13. Burt, W. R.,, A. L. Underwood, and, G. L. Appleton. 1981. Hydroxamic acid from Histoplasma capsulatum that displays growth factor activity. Appl. Environ. Microbiol. 42:560563.
14. Cano, M. V. C., and, R. A. Hajjeh. 2001. The epidemiology of histoplasmosis: a review. Semin. Respin. Infect. 16:109118.
15. Davis, C. G. 1990. The many faces of epidermal growth factor repeats. New Biol. 2:410419.
16. Deepe, G. S., Jr. 2000. Immune response to early and late Histoplasma capsulatum infections. Curr. Opin. Microbiol. 3:359362.
17. Deepe, G. S., Jr.,, R. Gibbons,, G. D. Brunner, and, F. J. Gomez. 1996. A protective domain of heat-shock protein 60 from Histoplasma capsulatum. J. Infect. Dis. 174:828834.
18. Deepe, G. S., Jr., and, R. A. Seder. 1998. Molecular and cellular determinants of immunity to Histoplasma capsulatum. Res. Immunol. 149:397406.
19. Di Lallo, G.,, S. Gargano, and, B. Maresca. 1994. The Histoplasma capsulatum cdc2 gene is transcriptionally regulated during the morphologic transition. Gene 140:5157.
20. Eissenberg, L. G., and, W. E. Goldman. 1988. Fusion of lysosomes with phagosomes containing Histoplasma capsulatum: use of fluoresceinated dextran. Adv. Exp. Med. Biol. 239:5361.
21. Eissenberg, L. G.,, W. E. Goldman, and, P. H. Schlesinger. 1993. Histoplasma capsulatum modulates the acidification of phagolysosomes. J. Exp. Med. 177:16051611.
22. Eissenberg, L. G.,, S. Poirier, and, W. E. Goldman. 1996. Phenotypic variation and persistence of Histoplasma capsulatum yeasts in host cells. Infect. Immun. 64:53105314.
23. Eissenberg, L. G.,, J. L. West,, J. P. Woods, and, W. E. Goldman. 1991. Infection of P388D1 macrophages and respiratory epithelial cells by Histoplasma capsulatum: selection of avirulent variants and their potential role in persistent histoplasmosis. Infect. Immun. 59:16391646.
24. el-Rady, J., and, G. Shearer, Jr. 1996. Isolation and characterization of a calmodulin-encoding cDNA from the pathogenic fungus Histoplasma capsulatum. J. Med. Vet. Mycol. 34:163169.
25. el-Rady, J., and, G. Shearer, Jr. 1997. Cloning and analysis of an actin-encoding cDNA from the dimorphic pathogenic fungus Histoplasma capsulatum. J. Med. Vet. Mycol. 35:159166.
26. Finkel-Jimenez, B.,, M. Wuthrich, and, B. S. Klein. 2002. BAD1, an essential virulence factor of Blastomyces dermatitidis, suppresses host TNF-α production through TGF-β-dependent and -independent mechanisms. J. Immunol. 168:57465755.
27. Foster, L. A. 2002. Utilization and cell-surface binding of hemin by Histoplasma capsulatum. Can. J. Microbiol. 48:437442.
28. Gildea, L. A.,, R. E. Morris, and, S. L. Newman. 2001. Histoplasma capsulatum yeasts are phagocytosed via very late antigen-5, killed, and processed for antigen presentation by human dendritic cells. J. Immunol. 166:10491056.
29. Gomez, F. J.,, R. Allendoerfer, and, G. S. Deepe, Jr. 1995. Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis. Infect. Immun. 63:25872595.
30. Gomez, F. J.,, A. M. Gomez, and, G. S. Deepe, Jr. 1991. Protective efficacy of a 62-kilodalton antigen, HIS-62, from the cell wall and cell membrane of Histoplasma capsulatum yeast cells. Infect. Immun. 59:44594464.
31. Harris, G. S.,, E. J. Keath, and, J. Medoff. 1989. Expression of α- and β-tubulin genes during dimorphic-phase transitions of Histoplasma capsulatum. Mol. Cell. Biol. 9:20422049.
32. Hogan, L. H.,, S. Josvai, and, B. S. Klein. 1995. Genomic cloning, characterization, and functional analysis of the major surface adhesin WI-1 on Blastomyces dermatitidis yeasts. J. Biol. Chem. 270:3072530732.
33. Hogan, L. H., and, B. S. Klein. 1994. Altered expression of surface α-13-glucan in genetically related strains of Blastomyces dermatitidis that differ in virulence. Infect. Immun. 62:35433546.
34. Howard, D. H. 1999. Acquisition, transport, and storage of iron by pathogenic fungi. Clin. Microbiol. Rev. 12:394404.
35. Howard, D. H.,, N. Dabrowa,, V. Otto, and, J. Rhodes. 1980. Cysteine transport and sulfite reductase activity in a germination-defective mutant of Histoplasma capsulatum. J. Bacteriol. 141:417421.
36. Howard, D. H.,, R. Rafie,, A. Tiwari, and, K. F. Faull. 2000. Hydroxamate siderophores of Histoplasma capsulatum. Infect. Immun. 68:23382343.
37. Hwang, L.,, D. Hocking-Murray,, A. K Bahrami,, M. Andersson,, J. Rine, and, A. Sil. 2003. Identifying phase-specific genes in the fungal pathogen Histoplasma capsulatum using a genomic shotgun microarray. Mol. Biol. Cell 14:23142326.
38. Kasuga, T.,, T. J. White,, G. Koenig,, J. McEwen,, A. Restrepo,, E. Castaneda,, C. da Silva Lacaz,, E. M. Heins-Vaccari,, R. S. de Freitas,, R. M. Zancope-Oliveira,, Z. Qin,, R. Negroni,, D. A. Carter,, Y. Mikami,, M. Tamura,, M. L. Taylor,, G. F. Miller,, N. Poonwan, and, J. W. Taylor. 2003. Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol. Ecol. 12:33833401.
39. Keath, E. J., and, F. E. Abidi. 1994. Molecular cloning and sequence analysis of yps-3, a yeast phase-specific gene in the dimorphic fungal pathogen Histoplasma capsulatum. Microbiology 140:759767.
40. Keath, E. J.,, G. S. Kobayashi, and, G. Medoff. 1992. Typing of Histoplasma capsulatum by restriction fragment length polymorphisms in a nuclear gene. J. Clin. Microbiol. 30:21042107.
41. Keath, E. J.,, A. A. Painter,, G. S. Kobayashi, and, G. Medoff. 1989. Variable expression of a yeast-phase-specific gene in Histoplasma capsulatum strains differing in thermotolerance and virulence. Infect. Immun. 57:13841390.
42. Klein, B. S. 2000. Molecular basis of pathogenicity in Blastomyces dermatitidis: the importance of adhesion. Curr. Opin. Microbiol. 3:339343.
43. Klimpel, K. R., and, W. E. Goldman. 1987. Isolation and characterization of spontaneous avirulent variants of Histoplasma capsulatum. Infect. Immun. 55:528533.
44. Klimpel, K. R., and, W. E. Goldman. 1988. Cell walls from avirulent variants of Histoplasma capsulatum lack α-(1, 3)-glucan. Infect. Immun. 56:29973000.
45. Kügler, S.,, T. S. Sebghati,, L. G. Eissenberg, and, W. E. Goldman. 2000. Phenotypic variation and intracellular parasitism by Histoplasma capsulatum. Proc. Natl. Acad. Sci. USA 97:87948798.
46. Kügler, S.,, B. Young,, V. L. Miller, and, W. E. Goldman. 2000. Monitoring phase-specific gene expression in Histoplasma capsulatum with telomeric GFP fusion plasmids. Cell. Microbiol. 2:537547.
47. Kwon-Chung, K. J. 1972. Emmonsiella capsulata : perfect state of Histoplasma capsulatum. Science 177:368369.
48. Kwon-Chung, K. J. 1973. Studies on Emmonsiella capsulata. I. Heterothallism and development of the ascocarp. Mycologia 65:109121.
49. Kwon-Chung, K.,, R. J. Weeks, and, H. W. Larsh. 1974. Studies on Emmonsiella capsulata (Histoplasma capsulatum). II. Distribution of the two mating types in 13 endemic states of the United States. Am. J. Epidemiol. 99:4449.
50. Lane, T. E.,, B. A. Wu-Hsieh, and, D. H. Howard. 1991. Iron limitation and the gamma interferon-mediated anti-histoplasma state of murine macrophages. Infect. Immun. 59:22742278.
51. Lane, T. E.,, B. A. Wu-Hsieh, and, D. H. Howard. 1993. Gamma interferon cooperates with lipopolysaccharide to activate mouse splenic macrophages to an antihisto-plasma state. Infect. Immun. 61:14681473.
52. Lesuisse, E., and, P. Labbe. 1989. Reductive and non-reductive mechanisms of iron assimilation by the yeast Saccharomyces cerevisiae. J. Gen. Microbiol. 135:257263.
53. Long, K. H.,, F. J. Gomez,, R. E. Morris, and, S. L. Newman. 2003. Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J. Immunol. 170:487494.
54. Medoff, J.,, E. Jacobson, and, G. Medoff. 1981. Regulation of dimorphism in Histoplasma capsulatum by cyclic AMP. J. Bacteriol. 145:14521455.
55. Medoff, G.,, G. S. Kobayashi,, A. Painter, and, S. Travis. 1987. Morphogenesis and pathogenicity of Histoplasma capsulatum. Infect. Immun. 55:13551358.
56. Medoff, G.,, M. Sacco,, B. Maresca,, D. Schlessinger,, A. Painter,, G. S. Kobayashi, and, L. Carratu. 1986. Irreversible block of the mycelial-to-yeast phase transition of Histoplasma capsulatum. Science 231:476479.
57. Newman, S. L.,, C. Bucher,, J. Rhodes, and, W. E. Bullock. 1990. Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion. J. Clin. Investig. 85:223230.
58. Newman, S. L.,, S. Chaturvedi, and, B. S. Klein. 1995. The WI-1 antigen of Blastomyces dermatitidis yeasts mediates binding to human macrophage CD11b/CD18 (CR3) and CD14. J. Immunol. 154:753761.
59. Newman, S. L.,, L. Gootee,, G. Brunner, and, G. S. Deepe, Jr. 1994. Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J. Clin. Investig. 93:14221429.
60. Newman, S. L.,, L. Gootee,, C. Kidd,, G. M. Ciraolo, and, R. Morris. 1997. Activation of human macrophage fungistatic activity against Histoplasma capsulatum upon adherence to type 1 collagen matrices. J. Immunol. 158:17791786.
61. Newman, S. L.,, L. Gootee,, R. Morris, and, W. E. Bullock. 1992. Digestion of Histoplasma capsulatum yeasts by human macrophages. J. Immunol. 149:574580.
62. Newman, S. L.,, L. Gootee,, V. Stroobant,, H. van der Goot, and, J. R. Boelaert. 1995. Inhibition of growth of Histoplasma capsulatum yeast cells in human macrophages by the iron chelator VUF 8514 and comparison of VUF 8514 with deferoxamine. Antimicrob. Agents Chemother. 39:18241829.
63. Nyhus, K. J.,, A. T. Wilborn, and, E. S. Jacobson. 1997. Ferric iron reduction by Cryptococcus neoformans. Infect. Immun. 65:434438.
64. Patel, J. B.,, J. W. Batanghari, and, W. E. Goldman. 1998. Probing the yeast phase-specific expression of the CBP1 gene of Histoplasma capsulatum. J. Bacteriol. 180:17861792.
65. Rappleye, C. A.,, J. T. Engle, and, W. E. Goldman. 2004. RNA interference in Histoplasma capsulatum demonstrates a role for α-(1,3)-glucan in virulence. Mol. Microbiol. 53:153165.
66. Retallack, D. M., and, J. P. Woods. 1999. Molecular epidemiology, pathogenesis, and genetics of the dimorphic fungus Histoplasma capsulatum. Microbes Infect. 1:817825.
67. Rooney, P. J., and, B. S. Klein. 2004. Elements necessary for transcriptional activation of BAD1 in the yeast phase of Blastomyces dermatitidis. Eukaryot. Cell 3:785794.
68. Rooney, P. J.,, T. D. Sullivan, and, B. S. Klein. 2001. Selective expression of the virulence factor BAD1 upon morphogenesis to the pathogenic yeast form of Blastomyces dermatitidis: evidence for transcriptional regulation by a conserved mechanism. Mol. Microbiol. 39:875889.
69. Sacco, M.,, B. Maresca,, B. V. Kumar,, G. S. Kobayashi, and, G. Medoff. 1981. Temperature- and cyclic nucleotide-induced phase transitions of Histoplasma capsulatum. J. Bacteriol. 146:117120.
70. San-Blas, G.,, E. San-Blas,, E. Ormaechea, and, L. E. Serrano. 1977. Cell wall analysis of an adenine requiring mutant of the yeast-like form of Paracoccidiodes brasiliensis strain IVIC Pb9. Sabouraudia 15:297303.
71. San-Blas, G.,, F. San-Blas, and, L. E. Serrano. 1977. Host-parasite relationships in the yeastlike form of Paracoccidiodes brasiliensis strain IVIC Pb9. Infect. Immun. 15:343346.
72. Sebghati, T. S.,, J. T. Engle, and, W. E. Goldman. 2000. Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence. Science 290:13681372.
73. Spitzer, E.,, B. A. Lasker,, S. J. Travis,, G. S. Kobayashi, and, G. Medoff. 1989. Use of mitochondrial and ribosomal DNA polymorphisms to classify clinical and soil isolates of Histoplasma capsulatum. Infect. Immun. 57:14091412.
74. Steele, P. E.,, G. F. Carle,, G. S. Kobayashi, and, G. Medoff. 1989. Electrophoretic analysis of Histoplasma capsulatum chromosomal DNA. Mol. Cell. Biol. 9:983987.
75. Steenbergen, J. N.,, J. D. Nosanchuk,, S. D. Malliaris, and, A. Casadevall. 2004. Interaction of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum with Acanthamoeba castellanii. Infect. Immun. 72:34783488.
76. Strasser, J. E.,, S. L. Newman,, G. M. Ciraolo,, R. E. Morris,, M. L. Howell, and, G. E. Dean. 1999. Regulation of the macrophage vacuolar ATPase and phagosomelysosome fusion by Histoplasma capsulatum. J. Immunol. 162:61486154.
77. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddix,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser, and, D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 263:678681.
78. Taylor, M. L.,, M. E. Espinosa-Schoelly,, R. Iturbe,, B. Rico,, J. Casasola, and, F. Goodsaid. 1989. Evaluation of phagolysosome fusion in acridine orange stained macrophages infected with Histoplasma capsulatum. Clin. Exp. Immunol. 75:466470.
79. Tian, X., and, G. Shearer, Jr. 2002. The mold-specific MS8 gene is required for normal hypha formation in the dimorphic pathogenic fungus Histoplasma capsulatum. Eukaryo Cell 1:249256.
80. Timmerman, M. M., and, J. P. Woods. 1999. Ferric reduction is a potential iron acquisition mechanism for Histoplasma capsulatum. Infect. Immun. 67:64036408.
81. Timmerman, M. M., and, J. P. Woods. 2001. Potential role for extracellular glutathione-dependent ferric reductase in utilization of environmental and host ferric compounds by Histoplasma capsulatum. Infect. Immun. 69:76717678.
82. Vincent, R.,, R. Goewert,, W. E. Goldman,, G. S. Kobayashi,, A. M. Lambowitz, and, G. Medoff. 1986. Classification of Histoplasma capsulatum isolates by restriction fragment polymorphisms. J. Bacteriol. 165:813818.
83. Weaver, C. H.,, K. C. F. Sheehan, and, E. J. Keath. 1996. Localization of a yeast phase-specific gene product to the cell wall in Histoplasma capsulatum. Infect. Immun. 64:30483054.
84. Woods, J. P. 2002. Histoplasma capsulatum molecular genetics, pathogenesis, and responsiveness to its environment. Fungal Genet. Biol. 35:8197.
85. Woods, J. P.,, E. L. Heinecke,, J. W. Luecke,, E. Maldonado,, J. Z. Ng,, D. M. Retallack, and, M. M. Timmerman. 2001. Pathogenesis of Histoplasma capsulatum. Semin. Respir. Infect. 16:91101.

Tables

Generic image for table
Table 1.

Specific components implicated in pathogenesis

Citation: Woods J. 2006. Molecular Determinants of Pathogenesis, p 321-331. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch23

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