19-BBSRC-NSF/BIO Bacterial and host genetic factors contributing to microbiome acquisition and homeostatis in mosquitoes

Animals harbor gut microbial communities that are essential for their fitness. However, the mechanisms underlying how these communities assemble in the gut remain largely unexplored in most host systems. The proposed research builds on existing productive collaborations to expand our knowledge of how hosts control gut colonization by bacteria and, conversely, how bacteria adapt to the gut to form stable associations with hosts. To date, coevolution has almost exclusively been investigated in bacterial partners of highly stable, long-term associations such as obligate human pathogens or vertically transmitted obligate symbionts. Here, we hypothesize that host-microbiota coadaptation can also occur over repeated interactions spanning only very short time scales of the hosts' individual life span and is
likely mediated by genetic factors of both hosts and bacteria.

We will address our central hypothesis in the mosquito Aedes aegypti, an insect of interest because adult females can transmit Zika, dengue, and other arboviruses that cause severe disease in humans. Mosquitoes are an ideal system in which to test our hypothesis because they harbor simple gut communities containing bacterial taxa that can each be cultured and manipulated. Methods also exist to generate axenic (microbe-free) and gnotobiotic mosquitoes containing defined bacterial communities. Because both Ae. aegypti and its associated gut bacteria are genetically tractable, the proposed research provides a unique, in-depth mechanistic study of host-microbe gene interactions that are difficult to study in most systems.

The long-term goal of this proposal is to improve understanding of how hosts mediate gut colonization by bacteria and, conversely, how gut bacteria form stable associations with their hosts. Specifically, we plan to examine host-microbiota coadaptation in transient environments such as the guts of holometabolous insects, which are shed and replaced during molting and remodeled during metamorphosis. Our central hypothesis is that host-microbiota coadaptation can occur over very short time scales and is likely mediated by genetic factors of both hosts and symbionts. Our system of choice is the mosquito Aedes aegypti, a holometabolous insect that has long been studied for its medical relevance as the primary vector of arboviruses that cause severe disease in humans. This makes mosquitoes an ideal system in which to test our hypothesis as they represent a widely studied group of insects of ecological relevance and in which evolution spanning several host generations can be readily observed given their short generation time. Furthermore, mosquitoes offer a tractable system in which to examine host-gut microbiota interactions. Methods exist to generate axenic (microbe-free) and gnotobiotic mosquitoes containing defined bacterial communities, and we have developed systems to genetically alter both the host and microbiota, enabling us to disentangle host-microbe and microbe-microbe interactions. The proposed research integrates high-throughput genomics and transcriptomics approaches with experimental studies of host and bacterial gene function and coevolution, and thus provides a unique, in-depth mechanistic study of host-symbiont interactions at maximum resolution.