Identification of Drosophila Mutants Affecting Defense to an Entomopathogenic Fungus.

Hsiao-Ling Lu,Jonathan B Wang,Raymond J St Leger,Markus A Brown,Christopher Euerle

doi:10.1038/srep12350

Hsiao-Ling Lu, Jonathan B Wang + Show 3 more

Open Access

https://doi.org/10.1038/srep12350

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Journal: Scientific Reports	Publication Date: Jul 23, 2015
Citations: 38	License type: CC BY 4.0

Affiliation: University of Maryland, College Park

Abstract

Fungi cause the majority of insect disease. However, to date attempts to model host–fungal interactions with Drosophila have focused on opportunistic human pathogens. Here, we performed a screen of 2,613 mutant Drosophila lines to identify host genes affecting susceptibility to the natural insect pathogen Metarhizium anisopliae (Ma549). Overall, 241 (9.22%) mutant lines had altered resistance to Ma549. Life spans ranged from 3.0 to 6.2 days, with females being more susceptible than males in all lines. Speed of kill correlated with within-host growth and onset of sporulation, but total spore production is decoupled from host genotypes. Results showed that mutations affected the ability of Drosophila to restrain rather than tolerate infections and suggested trade-offs between antifungal and antibacterial genes affecting cuticle and gut structural barriers. Approximately, 13% of mutations where in genes previously associated with host pathogen interactions. These encoded fast-acting immune responses including coagulation, phagocytosis, encapsulation and melanization but not the slow-response induction of anti-fungal peptides. The non-immune genes impact a wide variety of biological functions, including behavioral traits. Many have human orthologs already implicated in human disorders; while others were mutations in protein and non-protein coding genes for which disease resistance was the first biological annotation.

Highlights

The fruit fly Drosophila melanogaster has been the model of choice to develop ideas about innate immunity and host–pathogen interactions[1,2], but much of what we know has been deciphered using opportunistic human pathogens stabbed or injected into immunocompromised flies
Fungi cause the majority of insect disease[4], and include species such as Metarhizium anisopliae that are naturally pathogenic to Drosophila
This renders M. anisopliae much more amenable to screening than opportunistic human fungal pathogens that have to be injected into the hemocoel to cause infection, and allowed us to study the whole suite of host defenses that the fly is able to mount

Summary

Introduction

The fruit fly Drosophila melanogaster has been the model of choice to develop ideas about innate immunity and host–pathogen interactions[1,2], but much of what we know has been deciphered using opportunistic human pathogens stabbed or injected into immunocompromised flies These studies model septic injuries but by bypassing the initial steps of cuticular penetration they may not be appropriate models to study commonly occurring insect pathogens[3]. Unlike viruses and bacteria that normally infect through the oral route, M. anisopliae breaches the cuticle reaching directly into the hemocoel using a combination of mechanical pressure and an array of cuticle-degrading enzymes[5] This renders M. anisopliae much more amenable to screening than opportunistic human fungal pathogens that have to be injected into the hemocoel to cause infection, and allowed us to study the whole suite of host defenses that the fly is able to mount. This study establishes a foundation for understanding the genes imparting Drosophila’s resistance to a natural fungal pathogen, and will allow the identification of gene networks that may be specific to M. anisopliae infection, to insect pathogenic fungi in general, or to a variety of opportunistic mammalian pathogens

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