Ant brain metabolomics reveals contrasting purine and amine dynamics in a reversible trematode-induced host manipulation

Abstract The neurochemical mechanisms underlying parasite-induced host manipulations remain poorly understood. Formicid ants infected with lancet fluke, Dicrocoelium dendriticum, attach to vegetation with their mandibles during cool conditions, facilitating ingestion by grazing mammals—the obligate definitive host. Following several hours of attachment, ants detach, return to their nests, then repeat the attach/detach sequence on subsequent days. To investigate the molecular basis of this reversible manipulation, we used targeted and untargeted metabolomics to compare the brain chemistry of infected and uninfected field-collected ants during four sequential phases of manipulation. Targeted analysis of biogenic amines showed that tyramine and serotonin concentrations were 16% and 22% lower, respectively, in infected versus uninfected ants, but only during the detachment phase. Untargeted metabolomics revealed that the purine adenosine was 190% higher in infected ants during attachment. This result implicates the adenosine pathway, a key regulator of insect sleep/wake cycles, feeding inhibition and immune responsiveness, in the induction of the immobile, biting phase. Taurine levels were also reduced in the infected ants, potentially suppressing eusocial behaviours such as nest leaving. These results suggest that D. dendriticum uses distinct neurochemical mechanisms to orchestrate contrasting phases of manipulation: adenosine-mediated induction of attachment and biogenic amine-mediated regulation of detachment.