Determination of Growth-Coupling Strategies and Their Underlying Principles

Many insects of medical and agricultural importance depend on symbiotic associations with nutrient producing bacteria. Very commonly, net nutrient production by the bacteria is dictated by metabolic competition and cooperation among multiple bacterial taxa and strongly influenced by the metabolites derived from the insect host, but the mechanistic details of the multi-way metabolic interactions are poorly understood. To investigate the processes shaping insect-microbe metabolic interactions and to derive estimates of the composition and amount of nutrients exchanged between insect and microbe, we reconstructed genome and transcriptome-informed metabolic models of sap-feeding insects that harbor intracellular bacterial partners and the bacterial community in the Drosophila gut. Our simulations reveal that among intracellular bacterial partners the insect host controls bacterial production of nutrients, by precise controls over the concentrations of substrate metabolites in essential nutrient biosynthetic pathways. The net result is the structuring of the metabolic networks of the bacteria, to promote cooperative cross-feeding of metabolites and minimize competition for host-derived substrates. Among gut microbes competitive interactions dominate and the quality and quantity of nutrients available to the host is influenced by the composition of gut microbiota which synthesize and consume host and microbe derived nutrients. Our studies elucidate the metabolic basis of insect-microbe interactions and provide the methodology to identify specific gene targets for novel pest control strategies and to select the optimal microbial consortia for personalized microbial therapies in treating animal diseases associated with microbial dysbiosis.