Characterizing the Influence of Resident Microbiota and Mosquito Factors on Plasmodium Infections of Anopheles Mosquitoes
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AbstractPathogens transmitted by mosquitoes are responsible for illnesses that cause nearly 700 million cases every year. A significant proportion of this morbidity is due to malaria, a disease caused by Plasmodium parasites and spread through the bites of infected Anopheles mosquitoes. While we have seen a reduction in malaria mortality rates thanks to the development of antimalarial therapeutics and entomological controls, there is a potential of malaria resurgence associated with the emergence and spread of antimalarial and insecticide resistance, highlighting the need for additional malaria control strategies. Malaria transmission occurs only if one Plasmodium parasite develops through key stages in the mosquito, including passing through the midgut, which harbors a microbial community that can influence Plasmodium transmission. Despite the opportunities they present for novel interventions, the development of Plasmodium sporozoites and the factors that shape the microbiota in mosquitoes are incompletely understood. Here, I sought to provide new insights into the microbial variations of wild-caught mosquitoes and the transcriptional regulatory programs of Plasmodium sporozoites. To this end, I simultaneously characterized the bacterial composition of 665 individual field-caught Anopheles mosquitoes in addition to their species, insecticide resistance genotype, blood-meal status, and infection status. My analyses revealed that mosquito collection site is the main driver of the microbial diversity, while other factors showed marginal or non-significant contribution. I also generated scRNA-seq data from 36,958 sporozoites of three Plasmodium species and collected from multiple anatomical sites of the mosquito and developmental stages of the parasite in an effort to better understand parasite developmental processes critical for malaria transmission. I identified transcriptional variations among salivary gland sporozoites of different Plasmodium species, patterns of gene regulation accompanying the journey of Plasmodium berghei sporozoites, and novel candidates potentially critical for mechanisms involved in sporozoite maturation. In addition, my analyses highlighted novel extensive transcriptional heterogeneity among sporozoites isolated from the same anatomical site, indicating asynchronous sporozoite development in the mosquito, that is regulated by intrinsic and environmental factors. Altogether, my findings improve our understanding of factors that influence malaria parasite transmission and lay the groundwork for identifying key transmission components, to inform development of novel intervention strategies.
University of Maryland, Baltimore