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Massively parallel screening of synthetic microbial communities

Jared Kehe,Anthony B. Kulesa,7 Authors,P. Blainey

2019 · DOI: 10.1073/pnas.1900102116
Proceedings of the National Academy of Sciences of the United States of America · 230 Citations

TLDR

The kChip is introduced, a droplets-based platform that performs rapid, massively parallel, bottom-up construction and screening of synthetic microbial communities and enables phenotypic characterization of microbes across environmental conditions.

Abstract

Significance Microbial communities have many applications, but current experimental strategies to investigate their behavior are limited by the combinatorial complexity of interactions between species. Here, we introduce a platform to automatically construct and test synthetic communities of microbes from a set of input species at a scale of ∼100,000 communities per day. As a first demonstration, we discovered specific compositions of bacteria isolated from local soil that promote the growth of a model plant symbiont. More broadly, our platform can be adopted for the discovery of microbial consortia with many useful properties, such as suppression of pathogens or degradation of recalcitrant substrates for use in biofuel production or environmental remediation. Microbial communities have numerous potential applications in biotechnology, agriculture, and medicine. Nevertheless, the limited accuracy with which we can predict interspecies interactions and environmental dependencies hinders efforts to rationally engineer beneficial consortia. Empirical screening is a complementary approach wherein synthetic communities are combinatorially constructed and assayed in high throughput. However, assembling many combinations of microbes is logistically complex and difficult to achieve on a timescale commensurate with microbial growth. Here, we introduce the kChip, a droplets-based platform that performs rapid, massively parallel, bottom-up construction and screening of synthetic microbial communities. We first show that the kChip enables phenotypic characterization of microbes across environmental conditions. Next, in a screen of ∼100,000 multispecies communities comprising up to 19 soil isolates, we identified sets that promote the growth of the model plant symbiont Herbaspirillum frisingense in a manner robust to carbon source variation and the presence of additional species. Broadly, kChip screening can identify multispecies consortia possessing any optically assayable function, including facilitation of biocontrol agents, suppression of pathogens, degradation of recalcitrant substrates, and robustness of these functions to perturbation, with many applications across basic and applied microbial ecology.