ABSTRACT:Probiotics have been used to protect hosts from pathogens of gastrointestinal and reproductive systems, but their ability to protect against systemic pathogens is largely unexplored. In this study we ask whether orally administered bacteria and yeasts can protect Drosophila melanogaster against the opportunistic fungal pathogen Aspergillus flavus. Flies were fed an artificial diet mixed with live microorganisms for one day prior to infection with A. flavus, and mortality was recorded every day for 8 days. Seven microorganisms were tested; of these, Bacillus cereus (ATCC 13061), Candida inconspicua, Issatchenkia hanoiensis, and Klebsiella sp. significantly decreased mortality of flies subsequently infected with A. flavus compared to controls infected with A. flavus alone. Heat-killed microorganisms did not protect flies, suggesting that the probiotic effect observed was not caused by improved nutrition. D. melanogaster is a good model organism to study microbial interactions with hosts and test the effects of potential probiotics against pathogens.