Novel Symbiotic Genome-Scale Model Reveals Wolbachia 's Arboviral Pathogen Blocking Mechanism in Aedes aegypti

are endosymbiont bacteria known to infect arthropods causing different effects, such as cytoplasmic incompatibility and pathogen blocking in Aedes aegypti. Although several strains have been studied, there is little knowledge regarding the relationship between this bacterium and their hosts, particularly on their obligate endosymbiont nature and its pathogen blocking ability. Motivated by the potential applications on disease control, we developed a genome-scale model of two strains: Mel and the strongest Dengue blocking strain known to date: MelPop. The obtained metabolic reconstructions exhibit an energy metabolism relying mainly on amino acids and lipid transport to support cell growth that is consistent with altered lipid and cholesterol metabolism in -infected mosquitoes. The obtained metabolic reconstruction was then coupled with a reconstructed mosquito model to retrieve a symbiotic genome-scale model accounting for 1,636 genes and 6,408 reactions of the Aedes aegypti- interaction system. Simulation of an arboviral infection in the obtained novel symbiotic model represents a metabolic scenario characterized by pathogen blocking in higher titer strains, showing that pathogen blocking by infection is consistent with competition for lipid and amino acid resources between arbovirus and this endosymbiotic bacteria. Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of as an approach for disease control has motivated new research related to the characterization of the mechanisms that underlie its pathogen-blocking properties. In this work, we propose a new approach for studying the metabolic interactions between Aedes aegypti and using genome-scale models, finding that pathogen blocking is mainly influenced by competition for the resources required for and viral replication.