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Various parasite-host interactions that involve adaptive manipulation of host behavior display time-of-day synchronization of certain events. One example is the manipulated biting behavior observed in Carpenter ants infected with  Ophiocordyceps unilateralis sensu lato . We hypothesized that biological clocks play an important role in this and other parasite-host interactions. In order to identify candidate molecular clock components, we used two general strategies: bioinformatics and transcriptional profiling. The bioinformatics approach was used to identify putative homologs of known clock genes. For transcriptional profiling, RNA-Seq was performed on 48 h time courses of  Ophiocordyceps kimflemingiae  (a recently named species of the  O .  unilateralis  complex), whose genome has recently been sequenced. Fungal blastospores were entrained in liquid media under 24 h light-dark (LD) cycles and were harvested at 4 h intervals either under LD or continuous darkness. Of all  O .  kimflemingiae  genes, 5.3% had rhythmic mRNAs under these conditions (JTK Cycle, ≤ 0.057 statistical cutoff). Our data further indicates that a significant number of transcription factors have a peaked activity during the light phase (day time). The expression levels of a significant number of secreted enzymes, proteases, toxins and small bioactive compounds peaked during the dark phase or subjective night. These findings support a model whereby this fungal parasite uses its biological clock for phase-specific activity. We further suggest that this may be a general mechanism involved in parasite-host interactions.

Daily rhythms and enrichment patterns in the transcriptome of the behavior-manipulating parasite Ophiocordyceps kimflemingiae