Chapter 23 : Molecular Determinants of Pathogenesis

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Molecular Determinants of Pathogenesis, Page 1 of 2

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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
Restriction Fragment Length Polymorphism
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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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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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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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