The effects of sleep disruption, sex, and mating status on susceptibility to fungal ( Metarhizium anisopliae ) infections in Drosophila melanogaster

Important biological functions, including host defense, are linked to circadian rhythm and sleep. Studies have also indicated that the sex of the host can alter disease processes. In this study, we used a genetic approach in Drosophila to determine how sleep interacts with sex to influence the outcomes of infection with Metarhizium anisopliae strain Ma549. We found that as in mammals, Drosophila slept more after infection. The sleep-deprived Drosophila Shaker mutant with intact circadian rhythms failed to show this increased sleep response (sickness sleep) and succumbed quickly to infection. Mutants with disrupted PERIOD (PER) or CLOCK (CLK) affect circadian rhythms. The per ⁰¹ mutant shifted day/night cycles but not total sleep amounts, whereas the Clk ^Jrk mutant reduced sleep duration. Although mutations in per or Clk both impair sickness sleep, only per protects against disease, whereas active Clk reduces survival in infected Drosophila, which we attribute to it being pleiotropic. Independent of mutant status, males slept more than females, and virgins slept more than mated flies and survived infection longer, indicating that sex and mating status influence sleep and disease resistance irrespective of circadian rhythms.