Chapter 22 : Toward a Molecular Understanding of Virulence

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It is well known that putative virulence factors include adhesins, the secretion of hydrolytic enzymes, cellular morphogenesis, and phenotypic switching. In this chapter, the authors argue in favor of the recent suggestion that virulence factors are expressed at the cell surface and contribute directly to fungus-host interactions. However, the chapter also highlights the importance of fitness attributes for virulence. The overall aim must be to increase the precision with which the roles of specific virulence and fitness factors can be dissected. If the consequence of virulence is host damage and the aim is to assess the roles of specific molecular virulence factors in inflicting this damage, then experimental models of infection should permit quantification of such damage. The most widely used animal model of hematogenously disseminated infection (candidemia) involves intravenous challenge of mice with an inoculum that is lethal in virulent, wild-type strains. Its scientific advantage is that it offers high reproducibility and is currently by far the most widely used assay of virulence. One possible conclusion from the very large numbers of putative virulence factors discovered by gene disruption approaches is that is highly susceptible to the consequences of many different gene disruptions. Morphological interchange between yeast, pseudohyphal, and hyphal forms is one of the earliest recognized properties of .

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22

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Acetyl Coenzyme A
Cell Wall Proteins
Candida albicans
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Image of Figure 1.
Figure 1.

Temporal stages of infection in a mammalian host. Fungal cells (a) adhere to, and become commensal colonizers of, an epithelial surface (b). Given local deterioration in host defense, the fungi can penetrate epithelial layers (c); they may be able to invade as far as the bloodstream (d), leading to dissemination of fungal propagules, which may adhere to and penetrate vascular endothelia and thus gain access to deep tissues.

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22
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Table 1.

Notes on virulence assays in the murine intravenous-challenge model of disseminated infection

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22
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Table 2.

Notes on the construction of knockout mutants for virulence studies

Citation: Odds F, Gow N, Brown A. 2006. Toward a Molecular Understanding of Virulence, p 305-319. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch22

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