Journal Article

Syntrophic exchange in synthetic microbial communities

Church, George M., Collins, James J., Wang, Harris H., Mee, Michael T.

2014

Overview

Metabolic exchange between microbes is a crucial process driving the development of microbial ecosystems. The exchange of essential amino acids presents an opportunity to investigate the guiding principles underlying microbial trade in nature. In this study, we devised synthetic communities of Escherichia coli bacteria of increasing complexity to measure general properties enabling metabolic exchange of amino acids. We identified numerous syntrophic interactions that enable cooperative growth, which exhibited both positive and negative epistasis with increasing community complexity. Our results suggest that amino acid auxotrophy may be an evolutionarily optimizing strategy to reduce biosynthetic burden while promoting cooperative interactions between different bacteria in the microbiome. 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Amino acids / Amino Acids - biosynthesis / Amino Acids, Essential - biosynthesis / arginine / aromatic compounds / bacteria / Bacteria - genetics / Bacteria - metabolism / Biological Sciences / Biosphere / Biosynthesis / Biotechnology / Coculture Techniques / E coli / Ecology / Ecosystem / epistasis / Escherichia coli / Escherichia coli - genetics / Escherichia coli - metabolism / evolution / Gene Expression Regulation, Bacterial / genomics / isoleucine / Keystone species / lysine / methionine / Microbial activity / microbial communities / Microbial Interactions / Models, Biological / Phylogeny / PNAS Plus / PNAS Plus: Significance Statements / Temperature