Chapter 24 : Molecular Determinants of Virulence in

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The opportunistic pathogen is a ubiquitous fungus that can cause diseases that range in severity from mild allergic rhinitis to life-threatening invasive pulmonary and disseminated infection. The importance of biosyntheses of primary metabolites for the growth of the fungus in host tissue has been addressed by a number of investigators. For example, -aminobenzoic acid-requiring mutants are nonpathogenic in a murine infection model of invasive pulmonary aspergillosis. Mutants of that lack a functional copy of are hypersensitive to the amino acid analog 5-methyltryptophan, which induces a starvation response in the wild type. In two different murine models, the Δ mutants display decreased virulence as measured by cumulative mortality and competitive growth. The production of elastinolytic proteinases was correlated with virulence in environmental and clinical isolates; the production of these enzymes during infection was demonstrated by detecting antibody responses to the enzymes in patients. Toxins of two classes have been studied for their contribution to the virulence of . Using the model to assay virulence, four clinical strains of and one of were compared for production of gliotoxin, growth rate, elastase and catalase activities, and virulence.

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24

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Murine Invasive Pulmonary Aspergillosis
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Image of Figure 1.
Figure 1.

Schematic representation of fungal DHN-melanin biosynthesis pathways (adapted from references and ). Probable reaction types are indicated ([O], oxidation; [H], reduction; –HO, dehydration). Arrows with dashed lines indicate probable reactions. CoA, coenzyme A.

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
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Image of Figure 2.
Figure 2.

Pentaketide-like melanin biosynthesis gene cluster of Adapted from reference .

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
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Image of Figure 3.
Figure 3.

Model of cAMP signal transduction in . Question marks indicate unverified components and reactions. Dashed arrows mark unverified relationships. Proteins deduced from cloned genes are labeled with circles shaded in gray. It is expected that cross talk between the cAMP regulatory network and other regulatory networks exists. Some of these potential interactions, which were deduced from current data, are indicated by questions marks. Adapted form reference .

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24
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Table 1.

gene deletion or disruption mutants reported to show a decrease in virulence

Citation: Rhodes J, Brakhage A. 2006. Molecular Determinants of Virulence in , p 333-345. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch24

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