Design of Orthogonal and Obligate Commensalism for Organism-Based Biological Containment

Biological containment is a critical safeguard for genetically engineered microbes prior to their environmental release to prevent proliferation in unintended regions. However, few biocontainment strategies can support the longer-term microbial survival that may be desired in a target environment without repeated human intervention. In addition, few strategies have been evaluated for their ability to function in the presence of other microbes. Here, we introduce the concept of an orthogonal and obligate commensalism for the autonomous creation of environments that are permissive for survival of a biocontained microbe. We show that this obligate commensalism is highly effective, with the survival of our commensal organism during co-culture dependent on the presence of our producer strain. We also show that this commensalism is orthogonal to a microbial consortium derived from maize root, with survival of the biocontained strain conditional upon the addition of the producer strain to the consortium. Overall, our study demonstrates a transition from a chemical to a biological dependence for biocontained organisms that could lay the groundwork for biocontained synthetic ecologies.