Aspergillosis in the fruit fly Drosophila melanogaster as a model system

Aspergillus flavus is one of the most important pathogenic fungi, responsible for about 30% of all aspergillosis cases in humans. Currently Drosophila melanogaster has emerged as a powerful alternative for aspergillosis studies.;Even though aspergillosis is well-characterized, issues regarding the virulence of A. flavus, defense gene in flies expressed against A. flavus, and the diversity of microorganisms in wild Drosophila with potential use as probiotics against aspergillosis are not well understood.;The main objective of this first chapter is to provide a brief background to put the following chapters in context. The second chapter is to study induced aspergillosis in flies to determine the virulence of A. flavus strains. Virulence of A. flavus was very variable, ranging from 15% to >90%. Clinical strains were significantly less virulent than environmental strains.;In the third chapter, I identify genes related to immune defense in flies that may help to provide insight into factors that lead to human aspergillosis. 1,081 of the 14,554 gene regions detected in flies not infected and infected with A. flavus strains of different virulence levels were significantly and differentially expressed. Some of these up/down-regulated genes were previously shown to be involved in defense responses against different pathogens.;In the fourth chapter I isolate microorganisms from wild Drosophila to elucidate diversity and richness as well as potential humans pathogens. 9 morphospecies of fungi and 12 morphospecies of bacteria were isolated from wild flies. The most abundant were the yeast Candida inconspicua and the bacterium Klebsiella sp. Species richness was higher in fungi but diversity was lower than in bacteria. We identified bacterial and fungal human pathogens in flies.;The fifth chapter uses microbes isolated from wild Drosophila and others as potential probiotics that help protect hosts against aspergillosis disease. Bacillus cereus (ATCC 13061), Issatchenkia hanoiensis and Candida inconspicua decreased mortality of flies infected with A. flavus. Heat-killed microorganisms did not protect flies.;The sixth chapter is dedicated to general conclusions of all the work described here. Drosophila melanogaster is an attractive model to answer what I proposed in this thesis dissertation.