Emergent cooperation in microbial metabolism

Wintermute, Edwin H.; Silver, Pamela A.

doi:10.1038/msb.2010.66

Cited by 321 publications

(350 citation statements)

References 30 publications

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“…Using quantitative PCR (qPCR) against the unique knockout chromosomal junction in each auxotrophic strain, we determined the relative abundance of each member of the pair (Dataset S2). In general, we did not find a significant relationship between coculture fold growth and the ratio between the pairwise consortium members, in contrast to previous results (14) (Fig. S2).…”

Section: Resultscontrasting

confidence: 99%

“…Understanding amino acid exchange therefore presents an opportunity to gain new insights into basic principles in metabolic crossfeeding. Recently, several studies have used model systems of Saccharomyces cerevisiae (12), Saccharomyces enterica (13), and E. coli (14)(15)(16) to study syntrophic growth of amino acid auxotrophs in coculture environments. Numerous quantitative models have also been developed to describe the behavior of these multispecies systems, including those that integrate dynamics (17,18), metabolism (19)(20)(21), and spatial coordination (22).…”

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confidence: 99%

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Syntrophic exchange in synthetic microbial communities

Mee

Collins

Church

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

507

549

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Metabolic crossfeeding is an important process that can broadly shape microbial communities. However, little is known about specific crossfeeding principles that drive the formation and maintenance of individuals within a mixed population. Here, we devised a series of synthetic syntrophic communities to probe the complex interactions underlying metabolic exchange of amino acids. We experimentally analyzed multimember, multidimensional communities of Escherichia coli of increasing sophistication to assess the outcomes of synergistic crossfeeding. We find that biosynthetically costly amino acids including methionine, lysine, isoleucine, arginine, and aromatics, tend to promote stronger cooperative interactions than amino acids that are cheaper to produce. Furthermore, cells that share common intermediates along branching pathways yielded more synergistic growth, but exhibited many instances of both positive and negative epistasis when these interactions scaled to higher dimensions. In more complex communities, we find certain members exhibiting keystone species-like behavior that drastically impact the community dynamics. Based on comparative genomic analysis of >6,000 sequenced bacteria from diverse environments, we present evidence suggesting that amino acid biosynthesis has been broadly optimized to reduce individual metabolic burden in favor of enhanced crossfeeding to support synergistic growth across the biosphere. These results improve our basic understanding of microbial syntrophy while also highlighting the utility and limitations of current modeling approaches to describe the dynamic complexities underlying microbial ecosystems. This work sets the foundation for future endeavors to resolve key questions in microbial ecology and evolution, and presents a platform to develop better and more robust engineered synthetic communities for industrial biotechnology.synthetic ecosystem | amino acid exchange | population modeling M icrobes are abundantly found in almost every part of the world, living in communities that are diverse in many facets. Although it is clear that cooperation and competition within microbial communities is central to their stability, maintenance, and longevity, there is limited knowledge about the general principles guiding the formation of these intricate systems. Understanding the underlying governing principles that shape a microbial community is key for microbial ecology but is also crucial for engineering synthetic microbiomes for various biotechnological applications (1-3). Numerous such examples have been recently described including the bioconversion of unprocessed cellulolytic feedstocks into biofuel isobutanol using fungal-bacterial communities (4) and biofuel precursor methyl halides using yeast-bacterial cocultures (5). Other emerging applications in biosensing and bioremediation against environmental toxins such as arsenic (6) and pathogens such as Pseudomonas aeruginosa and Vibrio cholerae have been demonstrated using engineered quorum-sensing Escherichia coli (7, 8). These ...

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Section: Resultscontrasting

confidence: 99%

mentioning

confidence: 99%

Syntrophic exchange in synthetic microbial communities

Mee

Collins

Church

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

507

549

View full text Add to dashboard Cite

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“…This finding suggests that both auxotrophic and cross-feeding phenotypes are likely common in natural populations of E. coli. The observation that many different pairs of single-gene deletion mutants of E. coli readily formed cooperative interactions (Wintermute and Silver, 2010) supports the view that the same mechanism likely also applies to other classes of metabolites. Moreover, similar phenomena may also be relevant in interspecific interactions.…”

Section: Distribution Of Obligate Cross-feeding Interactionssupporting

confidence: 59%

Fitness and stability of obligate cross-feeding interactions that emerge upon gene loss in bacteria

et al. 2013

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Cross-feeding interactions, in which bacterial cells exchange costly metabolites to the benefit of both interacting partners, are very common in the microbial world. However, it generally remains unclear what maintains this type of interaction in the presence of non-cooperating types. We investigate this problem using synthetic cross-feeding interactions: by simply deleting two metabolic genes from the genome of Escherichia coli, we generated genotypes that require amino acids to grow and release other amino acids into the environment. Surprisingly, in a vast majority of cases, cocultures of two cross-feeding strains showed an increased Darwinian fitness (that is, rate of growth) relative to prototrophic wild type cells-even in direct competition. This unexpected growth advantage was due to a division of metabolic labour: the fitness cost of overproducing amino acids was less than the benefit of not having to produce others when they were provided by their partner. Moreover, frequency-dependent selection maintained cross-feeding consortia and limited exploitation by non-cooperating competitors. Together, our synthetic study approach reveals ecological principles that can help explain the widespread occurrence of obligate metabolic cross-feeding interactions in nature.

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“…If the environment stops fluctuating, the same strain could be reprogrammed to have a unimodal distribution with every cell close to an optimal expression level to maximize growth and/or output of biosynthetic pathways 14,15 . Third, FABMOS-fim can create highly organized communities with distinct phenotypes to divide the effort of synthesizing 'costly' compounds 59,60 or separating incompatible biological processes (for example, nitrogen fixation and photosynthesis 13 ). Creating heterogeneous populations with cells performing different tasks can increase fitness and robustness 61 , result in more efficient use of resources 62 and enable cooperation that is essential for complex behaviours.…”

Section: Discussionmentioning

confidence: 99%

“…Creating heterogeneous populations with cells performing different tasks can increase fitness and robustness 61 , result in more efficient use of resources 62 and enable cooperation that is essential for complex behaviours. Because of these benefits, some synthetic biologists have advocated engineering microbial strains that live in communities 59,61 as they commonly do in nature (note: the communities do not have to have different species for them to be beneficial 13,57 ). The FABMOS-fim system could create these different phenotypes and regulate their ratio, rates of switching and gene expression levels.…”

Section: Discussionmentioning

confidence: 99%

Modulating the frequency and bias of stochastic switching to control phenotypic variation

et al. 2014

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Mechanisms that control cell-to-cell variation in gene expression ('phenotypic variation') can determine a population's growth rate, robustness, adaptability and capacity for complex behaviours. Here we describe a general strategy (termed FABMOS) for tuning the phenotypic variation and mean expression of cell populations by modulating the frequency and bias of stochastic transitions between 'OFF' and 'ON' expression states of a genetic switch. We validated the strategy experimentally using a synthetic fim switch in Escherichia coli. Modulating the frequency of switching can generate a bimodal (low frequency) or a unimodal (high frequency) population distribution with the same mean expression. Modulating the bias as well as the frequency of switching can generate a spectrum of bimodal and unimodal distributions with the same mean expression. This remarkable control over phenotypic variation, which cannot be easily achieved with standard gene regulatory mechanisms, has many potential applications for synthetic biology, engineered microbial ecosystems and experimental evolution.

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Emergent cooperation in microbial metabolism

Cited by 321 publications

References 30 publications

Syntrophic exchange in synthetic microbial communities

Syntrophic exchange in synthetic microbial communities

Fitness and stability of obligate cross-feeding interactions that emerge upon gene loss in bacteria

Modulating the frequency and bias of stochastic switching to control phenotypic variation

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