Designing metabolic division of labor in microbial communities

Thommes, Meghan; Wang, Taiyao; Zhao, Qi; Paschalidis, Ioannis Ch.; Segrè, Daniel

doi:10.1101/442376

Cited by 23 publications

(31 citation statements)

References 90 publications

(123 reference statements)

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“…At this stage, we can only speculate what such cooperative benefits might be, but one can imagine that cells might not only differ in methionine uptake, but also in a number of other metabolic traits 21 . If so, this could allow for some form of metabolic division of labor, where subpopulations exchange metabolites in the same way as synthetic bacterial communities can exchange amino acids 8,[68][69][70][71][72] . Exploring these and other potential benefits of the long-term phenotypic heterogeneity in methionine uptake is an exciting topic for future research.…”

Section: Discussionmentioning

confidence: 99%

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

2020

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Auxotrophy, the inability to produce an organic compound essential for growth, is widespread among bacteria. Auxotrophic bacteria rely on transporters to acquire these compounds from their environment. Here, we study the expression of both low-and high-affinity transporters of the costly amino acid methionine in an auxotrophic lactic acid bacterium, Lactococcus lactis. We show that the high-affinity transporter (Met-transporter) is heterogeneously expressed at low methionine concentrations, resulting in two isogenic subpopulations that sequester methionine in different ways: one subpopulation primarily relies on the high-affinity transporter (high expression of the Met-transporter) and the other subpopulation primarily relies on the low-affinity transporter (low expression of the Met-transporter). The phenotypic heterogeneity is remarkably stable, inherited for tens of generations, and apparent at the colony level. This heterogeneity results from a T-box riboswitch in the promoter region of the met operon encoding the high-affinity Met-transporter. We hypothesize that T-box riboswitches, which are commonly found in the Lactobacillales, may play as-yet unexplored roles in the predominantly auxotrophic lifestyle of these bacteria.

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Section: Discussionmentioning

confidence: 99%

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

2020

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“…Other molecular assays, particularly mass spectrometry (MS)-based proteomics, can be applied to strain-type either isolates or communities [110]. This is also true for MS-or NMRbased metabolomics or metabolic flux measurements [111]. Of course, microbial culture physiology and direct imaging has been used to differentiate among strains since the earliest microbiology, and in some cases, these timetested methods can be applied to communities as well.…”

Section: Strategies and Approaches To Identifying Community Strain DImentioning

confidence: 99%

Strain-level epidemiology of microbial communities and the human microbiome

et al. 2020

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The biological importance and varied metabolic capabilities of specific microbial strains have long been established in the scientific community. Strains have, in the past, been largely defined and characterized based on microbial isolates. However, the emergence of new technologies and techniques has enabled assessments of their ecology and phenotypes within microbial communities and the human microbiome. While it is now more obvious how pathogenic strain variants are detrimental to human health, the consequences of subtle genetic variation in the microbiome have only recently been exposed. Here, we review the operational definitions of strains (e.g., genetic and structural variants) as they can now be identified from microbial communities using different high-throughput, often culture-independent techniques. We summarize the distribution and diversity of strains across the human body and their emerging links to health maintenance, disease risk and progression, and biochemical responses to perturbations, such as diet or drugs. We list methods for identifying, quantifying, and tracking strains, utilizing highthroughput sequencing along with other molecular and "culturomics" technologies. Finally, we discuss implications of population studies in bridging experimental gaps and leading to a better understanding of the health effects of strains in the human microbiome.

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“…We showed that, in this controller architecture, there is a trade-off between robustness to environmental disturbances and robustness to perturbations in available resources to the genetic circuit. Placing different genetic circuit components in multiple cells has been proposed as a possible solution to relieve some resource sharing effects for larger genetic circuits [15], [21], [32]. However, our analysis shows that when fluctuations in cellular resources are considered, it is not possible to tune the population controller to be both robust to extracellular disturbances and to intracellular disturbances.…”

Section: Discussionmentioning

confidence: 88%

Trade-offs in Robustness to Perturbations of Bacterial Population Controllers

McBride

Vecchio

2020

Preprint

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Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell's pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controller's gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources.

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Designing metabolic division of labor in microbial communities

Cited by 23 publications

References 90 publications

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

Strain-level epidemiology of microbial communities and the human microbiome

Trade-offs in Robustness to Perturbations of Bacterial Population Controllers

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