Evidence that controls the timing of host death via its own circadian clock.

Timing in the natural world is a matter of life or death, consequently, nearly all life on Earth has evolved internal circadian clocks. Many behavior-manipulating parasites exhibit striking daily timing, but whether this is clock-driven has remained unclear. Here, we leveraged the laboratory-tractable zombie fruit fly model, infected by the behavior manipulating fungus , to tackle this long standing mystery. Using an automated behavioral paradigm, we found that the timing of death of wild-type flies continues to occur with ~21 hour periodicity in the absence of environmental cues. Surprisingly, we also discovered that light is required within the first 24 hours of exposure for to infect and kill flies. Experiments with circadian and photoreception mutants revealed that death is independent of host genotype, suggesting the fungus-not the host-drives this rhythm. Transcriptomic analysis of grown fungus revealed that maintains rhythmic gene expression independent of the fly host that peaks at sunset and has a free-running period of ~22 hours. Among cycling genes, we identified a transcript encoding a protein with high homology to , the blue light sensor and core component of the molecular oscillator in the model ascomycete fungus . Altogether, our findings suggest that has an endogenous circadian clock that it uses to control the timing of host death. This study provides evidence that a fungal clock can influence fly outcomes, pointing to a new mechanism by which parasites temporally coordinate host manipulation.