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Syntrophic splitting of central carbon metabolism in host cells bearing functionally different symbiotic bacteria

Abstract

Insects feeding on the nutrient-poor diet of xylem plant sap generally bear two microbial symbionts that are localized to different organs (bacteriomes) and provide complementary sets of essential amino acids (EAAs). Here, we investigate the metabolic basis for the apparent paradox that xylem-feeding insects are under intense selection for metabolic efficiency but incur the cost of maintaining two symbionts for functions mediated by one symbiont in other associations. Using stable isotope analysis of central carbon metabolism and metabolic modeling, we provide evidence that the bacteriomes of the spittlebug Clastoptera proteus display high rates of aerobic glycolysis, with syntrophic splitting of glucose oxidation. Specifically, our data suggest that one bacteriome (containing the bacterium Sulcia, which synthesizes seven EAAs) predominantly processes glucose glycolytically, producing pyruvate and lactate, and the exported pyruvate and lactate is assimilated by the second bacteriome (containing the bacterium Zinderia, which synthesizes three energetically costly EAAs) and channeled through the TCA cycle for energy generation by oxidative phosphorylation. We, furthermore, calculate that this metabolic arrangement supports the high ATP demand in Zinderia bacteriomes for Zinderia-mediated synthesis of energy-intensive EAAs. We predict that metabolite cross-feeding among host cells may be widespread in animal–microbe symbioses utilizing low-nutrient diets.

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Fig. 1: Images of insect used in this study and their dissected bacteriomes.
Fig. 2: Glucose-derived 13C incorporation into essential amino acid precursor metabolites.
Fig. 3: Comparison of intracellular and extracellular pyruvate and lactate 13C-label incorporation during 3-h incubation.
Fig. 4: Comparison of pyruvate and lactate release from Sulcia and Zinderia-spittlebug bacteriomes.
Fig. 5: Metabolic specialization in spittlebug bacteriomes.

Data availability

All models have been provided in three formats—SBML (.xml), MATLAB (.mat), and Excel (.xls)—and deposited in GitHub (https://github.com/na423/symbiosis_Warburg). SBML files of the models have also been submitted to the BioModels database [53] with the following identifiers: MODEL1908040002, MODEL1908040003, and MODEL1908040004.

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Acknowledgements

We thank Seung Ho Chung, Lu Liu, Frances Blow and Alyssa Bost for assistance with insect dissections, Jason Dombroskie (Cornell University Insect Collection) for assistance with insect identification, and Brandon Barker (Aristotle Cloud Federation) for assistance with virtual machine image development, made possible by National Science Foundation grant ACI-1541215. This study was funded by NSF grant IOS-1354743 awarded to A.E.D., and a NSF CAREER grant (CBET-1653092) awarded to L.A. Graduate support for RAW was also provided by the NSF Graduate Research Fellowship Program (DGE-1650441).

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NYDA, LA, and AED designed research; NYDA, FZ, DZ, and TK performed research; RAW and LA performed mass spectrometry analysis; NYDA created the models and performed model analysis, NYDA analyzed data; NYDA and AED wrote the first draft of the paper; paper revisions made by all authors.

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Correspondence to Ludmilla Aristilde or Angela E. Douglas.

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Ankrah, N.Y.D., Wilkes, R.A., Zhang, F.Q. et al. Syntrophic splitting of central carbon metabolism in host cells bearing functionally different symbiotic bacteria. ISME J 14, 1982–1993 (2020). https://doi.org/10.1038/s41396-020-0661-z

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