Decoding the language of transmission among vector-pathogen-host

Abstract

Vector-borne diseases account for over 17 percent of all infectious diseases and lead to more than 700,000 mortalities annually. Importantly, there is a complex interaction between infectious organisms and their host. Vectors spread pathogens, which have a significant negative health effect on humans and animals and therefore detrimental economic and environmental impacts. Only 2% of the more than 3,600 mosquito species are blood feeders, primarily; the Anopheles, Culex, and Aedes which spread the Malaria parasite, Zika, Chikungunya, West Nile, and Dengue viruses. Therefore, understanding the complex chemical signaling and the molecular mechanisms that mediate pathogen and vector interaction, and allow the pathogen to survive and spread, are the subjects of this thesis.

In project I, we determined the production and release of Anopheles male aggregation Volatile Organic Compounds (VOCs) that initiate swarming, and enhance mating success. In addition, we compared the RNA-sequencing libraries of swarming to flag for chemosensory and circadian genes. The goal was to identify the molecular mechanisms of swarming and metabolite roles in mating success.

In project II, we evaluated the phagostimulant effects of (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) on an artificial feeding system for some important vectors (Anopheles coluzzii, An. arabiensis, An. gambiae s.s., Culex pipiens/Culex torrentium, and Aedes aegypti). We showed that our toxic plant-based solution can kill the five lethal vectors.

In project III, we studied the alteration of An. gambiae behavior by the Plasmodium falciparum at infected (oocyst-carrying, 7 days post-infection) and infective (sporozoite-carrying, 14 days post-infection) stages. To discover whether antennal chemosensory genes expression changes at different stages of infection, we performed RNA-seq and examined the candidate olfactory genes’ abundance to provide a possible molecular mechanism for manipulating the parasite-carrying mosquitoes' behavior.

Finally, in project IV, we presented the results of RNA-seq analysis that revealed the network connection between developmental genes and the physiological plasticity in male mosquitoes of An. funestus. We identified the transcripts that associated with the male An. funestus sexual maturation and mating success.

In summary, this thesis focuses on understanding how vector-pathogen interaction manipulates the vector’s transcriptome, physiology, and behavior to enhance transmission success and thereby identify novel targets for vector-borne disease control.