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Title: Designing Metabolic Division of Labor in Microbial Communities

Abstract

ABSTRACT Microbes face a trade-off between being metabolically independent and relying on neighboring organisms for the supply of some essential metabolites. This balance of conflicting strategies affects microbial community structure and dynamics, with important implications for microbiome research and synthetic ecology. A “gedanken” (thought) experiment to investigate this trade-off would involve monitoring the rise of mutual dependence as the number of metabolic reactions allowed in an organism is increasingly constrained. The expectation is that below a certain number of reactions, no individual organism would be able to grow in isolation and cross-feeding partnerships and division of labor would emerge. We implemented this idealized experiment using in silico genome-scale models. In particular, we used mixed-integer linear programming to identify trade-off solutions in communities of Escherichia coli strains. The strategies that we found revealed a large space of opportunities in nuanced and nonintuitive metabolic division of labor, including, for example, splitting the tricarboxylic acid (TCA) cycle into two separate halves. The systematic computation of possible solutions in division of labor for 1-, 2-, and 3-strain consortia resulted in a rich and complex landscape. This landscape displayed a nonlinear boundary, indicating that the loss of an intracellular reaction was not necessarily compensated formore » by a single imported metabolite. Different regions in this landscape were associated with specific solutions and patterns of exchanged metabolites. Our approach also predicts the existence of regions in this landscape where independent bacteria are viable but are outcompeted by cross-feeding pairs, providing a possible incentive for the rise of division of labor. IMPORTANCE Understanding how microbes assemble into communities is a fundamental open issue in biology, relevant to human health, metabolic engineering, and environmental sustainability. A possible mechanism for interactions of microbes is through cross-feeding, i.e., the exchange of small molecules. These metabolic exchanges may allow different microbes to specialize in distinct tasks and evolve division of labor. To systematically explore the space of possible strategies for division of labor, we applied advanced optimization algorithms to computational models of cellular metabolism. Specifically, we searched for communities able to survive under constraints (such as a limited number of reactions) that would not be sustainable by individual species. We found that predicted consortia partition metabolic pathways in ways that would be difficult to identify manually, possibly providing a competitive advantage over individual organisms. In addition to helping understand diversity in natural microbial communities, our approach could assist in the design of synthetic consortia.« less

Authors:
; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Boston Univ., MA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1505658
Alternate Identifier(s):
OSTI ID: 1610773
Grant/Contract Number:  
SC0004962; SC0012627
Resource Type:
Published Article
Journal Name:
mSystems
Additional Journal Information:
Journal Name: mSystems Journal Volume: 4 Journal Issue: 2; Journal ID: ISSN 2379-5077
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Microbiology

Citation Formats

Thommes, Meghan, Wang, Taiyao, Zhao, Qi, Paschalidis, Ioannis C., Segrè, Daniel, and Dutton, ed., Rachel J. Designing Metabolic Division of Labor in Microbial Communities. United States: N. p., 2019. Web. doi:10.1128/mSystems.00263-18.
Thommes, Meghan, Wang, Taiyao, Zhao, Qi, Paschalidis, Ioannis C., Segrè, Daniel, & Dutton, ed., Rachel J. Designing Metabolic Division of Labor in Microbial Communities. United States. doi:10.1128/mSystems.00263-18.
Thommes, Meghan, Wang, Taiyao, Zhao, Qi, Paschalidis, Ioannis C., Segrè, Daniel, and Dutton, ed., Rachel J. Tue . "Designing Metabolic Division of Labor in Microbial Communities". United States. doi:10.1128/mSystems.00263-18.
@article{osti_1505658,
title = {Designing Metabolic Division of Labor in Microbial Communities},
author = {Thommes, Meghan and Wang, Taiyao and Zhao, Qi and Paschalidis, Ioannis C. and Segrè, Daniel and Dutton, ed., Rachel J.},
abstractNote = {ABSTRACT Microbes face a trade-off between being metabolically independent and relying on neighboring organisms for the supply of some essential metabolites. This balance of conflicting strategies affects microbial community structure and dynamics, with important implications for microbiome research and synthetic ecology. A “gedanken” (thought) experiment to investigate this trade-off would involve monitoring the rise of mutual dependence as the number of metabolic reactions allowed in an organism is increasingly constrained. The expectation is that below a certain number of reactions, no individual organism would be able to grow in isolation and cross-feeding partnerships and division of labor would emerge. We implemented this idealized experiment using in silico genome-scale models. In particular, we used mixed-integer linear programming to identify trade-off solutions in communities of Escherichia coli strains. The strategies that we found revealed a large space of opportunities in nuanced and nonintuitive metabolic division of labor, including, for example, splitting the tricarboxylic acid (TCA) cycle into two separate halves. The systematic computation of possible solutions in division of labor for 1-, 2-, and 3-strain consortia resulted in a rich and complex landscape. This landscape displayed a nonlinear boundary, indicating that the loss of an intracellular reaction was not necessarily compensated for by a single imported metabolite. Different regions in this landscape were associated with specific solutions and patterns of exchanged metabolites. Our approach also predicts the existence of regions in this landscape where independent bacteria are viable but are outcompeted by cross-feeding pairs, providing a possible incentive for the rise of division of labor. IMPORTANCE Understanding how microbes assemble into communities is a fundamental open issue in biology, relevant to human health, metabolic engineering, and environmental sustainability. A possible mechanism for interactions of microbes is through cross-feeding, i.e., the exchange of small molecules. These metabolic exchanges may allow different microbes to specialize in distinct tasks and evolve division of labor. To systematically explore the space of possible strategies for division of labor, we applied advanced optimization algorithms to computational models of cellular metabolism. Specifically, we searched for communities able to survive under constraints (such as a limited number of reactions) that would not be sustainable by individual species. We found that predicted consortia partition metabolic pathways in ways that would be difficult to identify manually, possibly providing a competitive advantage over individual organisms. In addition to helping understand diversity in natural microbial communities, our approach could assist in the design of synthetic consortia.},
doi = {10.1128/mSystems.00263-18},
journal = {mSystems},
number = 2,
volume = 4,
place = {United States},
year = {2019},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1128/mSystems.00263-18

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