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Chapter 15 : Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis

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Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, Page 1 of 2

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Abstract:

A variety of human bacterial and fungal pathogens are highly virulent in diverse nonvertebrate hosts. This chapter focuses on three invertebrate systems that have been used to study human fungal pathogens. It first discusses two genetically tractable hosts: the fly and the microscopic nematode . Then it discusses the use of the greater wax moth caterpillar , which provides certain interesting technical advantages, even though it does not have a sequenced genome. The chapter briefly mentions other nonmammalian model hosts that have been used for the study of pathogenesis due to bacteria or parasites, which workers may wish to consider for the study of fungal pathogens. One of the exciting aspects of the model is that it can be used to screen libraries of random mutants in order to identify hypovirulent mutants that can then be evaluated in mammalian models. The similarities between microbial pathogenesis in mammalian models and host-pathogen interactions in alternative model hosts suggest that certain virulence aspects of these pathogens may have developed during the interaction of these microbes with environmental predators. In addition to providing a paradigm for understanding the origin and maintenance of fungal virulence, these models provide invaluable insights into host-pathogen interactions in general.

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15

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Figures

Image of Figure 1.
Figure 1.

Toll system response following fungal infection. A scanning electron micrograph shows a dead adult with a mutation involving the Toll pathway that succumbed to infection by and is covered with germinating hyphae. Wild-type flies are resistant to . Reprinted from reference with permission.

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
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Image of Figure 2.
Figure 2.

Algorithm outlining the approach for a screen of a mutant library of in . Of 350 mutants tested, 7 with attenuated virulence were identified through three screens, and the attenuation persisted after the mutation was crossed back into a wild-type strain. Genetic analysis of one strain revealed an insertion in a gene homologous to , which encodes a serine/threonine protein kinase. mutants exhibited significant defects in virulence in murine inhalation and hematogenous infection models and resulted in increased binding to alveolar and peritoneal macrophages. The mutant phenotypes were complemented by the wild-type gene ( ).

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
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Image of Figure 3.
Figure 3.

but not accumulates in the gastrointestinal tract of . (A) Intact yeast cells present in the distended gastrointestinal tract after feeding for 24 h on strain H99. (B) No cells can be detected in the gastrointestinal tract after 24 h of feeding. The round structure (white arrows) is the pharyngeal grinder organ, which functions to disrupt ingested organisms. Black and gray arrows point to the intestinal lumen. Reprinted from reference with permission.

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
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Tables

Generic image for table
Table 1.

Shortcomings associated with mammalian model systems for the study of microbial pathogenesis

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 2.

Advantages of using and for the study of pathogenesis

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 3.

Specific advantages and limitations of for the study of fungal pathogenesis

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 4.

Internet resources for the study of

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 5.

Specific advantages and limitations of for the study of fungal pathogenesis

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 6.

Internet resources for study of

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15
Generic image for table
Table 7.

Comparison of and systems for the study of pathogenesis

Citation: Mylonakis E, Calderwood S, Ausubel F. 2006. Heterologous Hosts and the Evolution and Study of Fungal Pathogenesis, p 215-225. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch15

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