Chemosensory Mechanisms Driving Malaria Transmission

About This Grant

To hunt humans and transmit malaria parasites, the African malaria mosquito Anopheles gambiae relies on its sense of smell to track volatile organic compounds emitted by the human body. Human body odor comprises a complex blend of hundreds of airborne chemicals derived from our primary metabolism released in skin odor and breath, as well as secondary metabolites produced by microbial communities living on our skin. Despite the important role of human body odor in driving malaria transmission, the specific components of human scent that blend together to modulate this process, as well as the relative contribution of the human skin microbiome towards human scent chemistry are not well understood. We have recently engineered and validated an expansive multi-choice system for Anopheles gambiae olfactory preference under naturalistic conditions in Zambia to rank the attractiveness of whole body scent samples derived from individual sleeping humans to mosquitoes using infrared motion vision. Leveraging this validated infrastructure and exposure-free assay with enhanced comparative power, we will recruit a cross-sectional human subjects cohort from the Macha region, Choma District, Southern Province, Zambia to identify volatile organic compounds in human scent signatures that are correlated with human attractiveness to Anopheles gambiae at high-resolution. In parallel, we will perform whole body microbiome profiling using metagenomics to characterize the contribution of the skin microbiome to human scent signatures. Using this approach, we will identify features of the human microbiome community and associated microbial metabolic pathways producing volatile organic compounds associated with modulating human attractiveness to this prolific disease vector. We will also harness conserved components of whole body odor, along with volatile organic compounds associated with high attractiveness that we have recently identified using whole body volatilomics, to reverse engineer super attractive synthetic chemical blends for Anopheles gambiae mimicking the scent signatures of highly attractive humans. These aims will fundamentally improve our understanding of chemosensory mechanisms modulating olfactory behavior in Anopheles gambiae that drive malaria transmission and influence heterogeneity in biting risk. From a translational perspective this research may assist to identify new biomarkers for personal risk of exposure to mosquito bites and develop novel synthetic formulations of attractants or repellents to combat this primary malaria vector in sub-Saharan Africa.