title: Cooperative Metabolism in a Three-Partner Insect-Bacterial Symbiosis Revealed by Metabolic Modeling.
abstract: An important factor determining the impact of microbial symbionts on their animal hosts is the balance between the cost of nutrients consumed by the symbionts and the benefit of nutrients released back to the host, but the quantitative significance of nutrient exchange in symbioses involving multiple microbial partners has rarely been addressed. In this study on the association between two intracellular bacterial symbionts, "CandidatusPortiera aleyrodidarum" and "CandidatusHamiltonella defensa," and their animal host, the whiteflyBemisia tabaci, we apply metabolic modeling to investigate host-symbiont nutrient exchange. Ourin silicoanalysis revealed that >60% of the essential amino acids and related metabolites synthesized by "CandidatusPortiera aleyrodidarum" are utilized by the host, including a substantial contribution of nitrogen recycled from host nitrogenous waste, and that these interactions are required for host growth. In contrast, "CandidatusHamiltonella defensa" retains most or all of the essential amino acids and B vitamins that it is capable of synthesizing. Furthermore, "CandidatusHamiltonella defensa" suppresses host growthin silicoby competition with "CandidatusPortiera aleyrodidarum" for multiple host nutrients, by suppressing "CandidatusPortiera aleyrodidarum" growth and metabolic function, and also by consumption of host nutrients that would otherwise be allocated to host growth. The interpretation from these modeling outputs that "CandidatusHamiltonella defensa" is a nutritional parasite could not be inferred reliably from gene content alone but requires consideration of constraints imposed by the structure of the metabolic network. Furthermore, these quantitative models offer precise predictions for future experimental study and the opportunity to compare the functional organization of metabolic networks in different symbioses.IMPORTANCEThe metabolic functions of unculturable intracellular bacteria with much reduced genomes are traditionally inferred from gene content without consideration of how the structure of the metabolic network may influence flux through metabolic reactions. The three-compartment model of metabolic flux between two bacterial symbionts and their insect host constructed in this study revealed that one symbiont is structured to overproduce essential amino acids for the benefit of the host, but the essential amino acid production in the second symbiont is quantitatively constrained by the structure of its network, rendering it "selfish" with respect to these nutrients. This study demonstrates the importance of quantitative flux data for elucidation of the metabolic function of symbionts. Thein silicomethodology can be applied to other symbioses with intracellular bacteria.
authors.affiliation: Department of Entomology, Cornell University, Ithaca, New York, USA.
authors.forename: Nana Y D
authors.initials: NYD
authors.lastname: Ankrah
authors.affiliation: Department of Entomology, Cornell University, Ithaca, New York, USA.
authors.forename: Junbo
authors.initials: J
authors.lastname: Luan
authors.affiliation: Department of Entomology, Cornell University, Ithaca, New York, USA aes326@cornell.edu.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Douglas
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D004755:Enterobacteriaceae / Q000502:physiology*; D044129:Halomonadaceae / Q000502:physiology*; D006430:Hemiptera / Q000382:microbiology*; D053858:Metabolic Networks and Pathways; D056265:Microbial Interactions; D009584:Nitrogen / Q000378:metabolism; D013559:Symbiosis
chemical_list: D000596:Amino Acids; D009584:Nitrogen
keywords: flux balance analysis; genome reduction; metabolic model; metabolic modeling; nutrient exchange; “Candidatus Hamiltonella defensa”; “Candidatus Portiera aleyrodidarum”