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Drosophila melanogaster as a model organism for invasive aspergillosis.

ABSTRACT: Mammalian hosts have traditionally been considered the "gold standard" models for studying pathogenesis and antifungal drug activity in invasive aspergillosis (IA). Nevertheless, logistical, economical, and ethical constraints make these host systems difficult to use for high-throughput screening of putative Aspergillus virulence factors and novel antifungal compounds. Here, we present Drosophila melanogaster, a heterologous non-vertebrate host with conserved innate immunity and genetic tractability, as an alternative, easy-to-use, and inexpensive pathosystem for studying Aspergillus pathogenesis and antifungal activity. We describe three different infection protocols (i.e., injection, rolling, ingestion) that introduce Aspergillus conidia at different anatomical sites of Toll-deficient Drosophila flies. These reproducible assays can be used to (1) determine the virulence of various Aspergillus strains and to (2) assess the anti-Aspergillus activity of orally absorbed antifungal agents in vivo. These methods can also be adapted to study pathogenesis and antifungal drug activity against other medically important human fungal pathogens.

SUBMITTER: Lionakis MS

PROVIDER: S-EPMC4045217 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Drosophila melanogaster as a model organism for invasive aspergillosis.

Lionakis Michail S MS Kontoyiannis Dimitrios P DP

Methods in molecular biology (Clifton, N.J.) 20120101

Mammalian hosts have traditionally been considered the "gold standard" models for studying pathogenesis and antifungal drug activity in invasive aspergillosis (IA). Nevertheless, logistical, economical, and ethical constraints make these host systems difficult to use for high-throughput screening of putative Aspergillus virulence factors and novel antifungal compounds. Here, we present Drosophila melanogaster, a heterologous non-vertebrate host with conserved innate immunity and genetic tractabi ...[more]

PMID: 22328395

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Project description:Epilepsy is one of the most prevalent neurological disorders, affecting more than 45 million people worldwide. Recent advances in genetic techniques, such as next-generation sequencing, have driven genetic discovery and increased our understanding of the molecular and cellular mechanisms behind many epilepsy syndromes. These insights prompt the development of personalized therapies tailored to the genetic characteristics of an individual patient. However, the surging number of novel genetic variants renders the interpretation of pathogenetic consequences and of potential therapeutic implications ever more challenging. Model organisms can help explore these aspects in vivo. In the last decades, rodent models have significantly contributed to our understanding of genetic epilepsies but their establishment is laborious, expensive, and time-consuming. Additional model organisms to investigate disease variants on a large scale would be desirable. The fruit fly Drosophila melanogaster has been used as a model organism in epilepsy research since the discovery of "bang-sensitive" mutants more than half a century ago. These flies respond to mechanical stimulation, such as a brief vortex, with stereotypic seizures and paralysis. Furthermore, the identification of seizure-suppressor mutations allows to pinpoint novel therapeutic targets. Gene editing techniques, such as CRISPR/Cas9, are a convenient way to generate flies carrying disease-associated variants. These flies can be screened for phenotypic and behavioral abnormalities, shifting of seizure thresholds, and response to anti-seizure medications and other substances. Moreover, modification of neuronal activity and seizure induction can be achieved using optogenetic tools. In combination with calcium and fluorescent imaging, functional alterations caused by mutations in epilepsy genes can be traced. Here, we review Drosophila as a versatile model organism to study genetic epilepsies, especially as 81% of human epilepsy genes have an orthologous gene in Drosophila. Furthermore, we discuss newly established analysis techniques that might be used to further unravel the pathophysiological aspects of genetic epilepsies.

Dataset Information

Drosophila melanogaster as a model organism for invasive aspergillosis.

Publications

Drosophila melanogaster as a model organism for invasive aspergillosis.

Similar Datasets

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