Geographic origin and sleep patterns predict disease outcomes in Drosophila melanogaster

Given the diversity in disease outcomes, even among closely related individuals, there is an urgent need to examine how defense is linked with other aspects of host physiology. The overall goal of this study was to employ Metarhizium anisopliae 549-Drosophila as a model system to examine how environmental and genetic factors influence fly survival across different biomes, as well as interactions between fungal infection, sleep, and host defense. We showed that resistance to Ma549 varies by sex and place of origin, with males and African lines usually being more resistant, and correlated with sleep parameters. Both the mean climate and climate extremes at collection sites, particularly tropical sites, were associated with disease resistance in the laboratory. Using representative fly lines, we found that daytime sickness sleep increased within the first two days post infection with Ma549, particularly in males of a line that were very resistant. Host defenses are linked to circadian rhythms in living organisms. Disrupted circadian rhythm can thus influence disease outcomes. Here, we employed a well-characterized sleep-deprived Drosophila Shaker mutant with intact circadian rhythms to confirm that sickness sleep contributes to enhanced survival. We also used two mutants with disrupted circadian clock-controlled genes to examine the role of the clock in activity and sickness sleep after Ma549 infection. Our data demonstrate that period and Shaker genes protect against disease, whereas active Clk^Jrk reduces survival in infected Drosophila.