Trypanosoma congolense manipulates the chemosensory system and behavior of Glossina pallidipes to enhance its transmission

The success of trypanosomes in transitioning between hosts and life stages depends on their ability to manipulate host metabolism, immunity, and behavior. Pathogen-favoring behaviors often link tsetse flies’ host behavioral plasticity and sensory adaptations, but the underlying mechanisms remain unclear. To uncover the molecular basis regulating neuronal sensitivity and transmission behavior in tsetse flies, we applied transcriptomics, metabolomics and validated by RT-qPCR and behavioral assays. Uninfected Glossina pallidipes were more attracted to Trypanosoma congolense-infected mice and metabolites from infected cow urine than to healthy ones. T. congolense infection alters host metabolic pathways, modifying the composition of volatile organic compounds in mice and cattle, which enhanced fly attraction. Infection modulated cellular signaling across multiple sensory modalities, including olfaction, vision, taste, thermosensation, and immunity in G. pallidipes. Trypanosome associated odors doubled the catch of infected G. pallidipes in the field, reducing infected flies by 75% and diseases prevalence in cattle by 40% based on agent-based model. These findings reveal the molecular interaction between T. congolense, G. pallidipes, and cattle, highlighting how the parasite manipulates multiple pathways to enhance adaptation, multiplication, and transmission. Muti-omics investigation reveals how trypanosomes manipulate their vertebrate host metabolites and tsetse flies’ multiple sensory modalities and immunity to enhance its survival and transmission.