Massively Parallel Screening of Synthetic Microbial Communities

By Dr. Katie E. Golden, MD

Microbial communities are emerging as an important area of research interest given their potential as biotechnological tools, with applications ranging from pharmaceuticals to agricultural development. One of the biggest challenges to engineering bacteria with specific benefits, however, is the inherent difficulty in predicting a species’ interactions with other microbial populations and the surrounding environment. To harness bacteria’s utility in biotechnological advances, and reverse-engineer communities with a specific purpose, we need to first develop the technology that can both capture and predict a bacteria’s dynamic nature.

In recently published research, Kehe outline a sophisticated tool that brilliantly performs rapid, large scale construction and analysis of synthetic microbial communities.1 Their work lays the critical foundation for the discovery and engineering of microbial consortia with beneficial properties. They call their novel technology kChip, which is a droplet-based platform that allows for parallel construction and screening of microbial combinations on an unprecedented scale.

To fully grasp the power of this technology, let’s first examine the conventional analysis of bacterial strains. As an example (outlined by the authors), let’s say you want to study a bacterial library of 16 strains. Using traditional pipetting techniques, a single experiment with just one medium would required about 160,000 liquid handling steps. These combinations have to be assembled in real-time given the time scale of cell-division and replication, and so generating data for even 10% of these combinations would be logistically impossible. Even under optimal conditions utilizing robotic technology, single studies can generate about 100 unique synthetic communities (and are typically restricted to binary compositions).

Now, let’s look at the kChip platform, which eliminates liquid handling and replaces it with nano-droplet technology. Each kChip unit contains tens of thousands of microwells, and each microwell is filled with randomly selected inputs (bacterial strains, media, etc) from a larger pre-selected library. This random combination of droplets is elegantly dictated by microwell geometry, thereby eliminating the time and logistic complexity of combination assembly. Each microwell is then exposed to an alternating-current electric field to combine their contents and ultimately generate parallel synthetic communities.  This system allows for the screening of approximately 100,000 communities per day, on a scale commensurate with natural ecological conditions.

To test their technology, the authors used the kChip to screen ~100,000 bacterial communities from soil, and were able to identify conditions that promote growth of a specific plant symbiont (a strain of interest). One can imagine the implications of similar experiments, for example, in identifying and developing probiotic interventions in microbial communities of the human intestine. With this new bio-engineering tool, scientists have unlocked a huge potential in understanding microbial community ecology and harnessing its potential for advances across multiple scientific and medical fields.

1. Massively parallel screening of synthetic microbial communities. Jared Kehe, Anthony Kulesa, Anthony Ortiz, Cheri M. Ackerman, Sri Gowtham Thakku, Daniel Sellers, Seppe Kuehn, Jeff Gore, Jonathan Friedman, Paul C. Blainey. Proceedings of the National Academy of Sciences Jun 2019, 116 (26) 12804-12809.