The biology of Anopheles mosquitoes has been heavily investigated due to their ability to transmit Plasmodium parasites that cause malaria. In particular, interactions between the mosquito immune system, Plasmodium parasites, and the endogenous midgut microbiota are critical determinants of the outcome of pathogen infection and transmission. In this regard, we have investigated bacteria-independent, Plasmodium-specific mosquito immune responses as well as the role fungi play in mosquito-pathogen interactions; two areas of research that have not been well studied. Using whole-genome transcript microarray analysis, RNAi-mediated gene silencing, Plasmodium infection assays, and other tools we reported two novel findings. First, we identified the existence of bacteria- and IMD pathway-independent anti-Plasmodium defenses. This finding highlights non-canonical anti-Plasmodium defenses that could be exploited to interrupt pathogen transmission. Second, we showed that the non-pathogenic fungus P. chrysogenum is capable of enhancing Plasmodium susceptibility in Anopheles mosquitoes. To our knowledge, this is the first report of a fungus capable of increasing Plasmodium infection, which has implications for the success of Plasmodium transmission in nature. Overall, we elucidated a novel immune mechanism as well as a new microbial component influencing mosquito-pathogen interactions.Keywords: Anopheles, immunity, Plasmodium, bacteria, fungi, microbiomeThesis Advisory Committee: Dr. George Dimopoulos, Dr. Marcelo Jacobs-Lorena, Dr. Petros Karakousis, and Dr. William MossAlternates: Dr. Douglas Norris and Dr. Michael Matunis
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MICROBIOME DEPENDENT AND INDEPENDENT DETERMINANTS OF PLASMODIUM INFECTION IN THE MOSQUITO ANOPHELES GAMBIAE