Horizontal gene transfer (HGT), and specifically plasmid conjugation, is a prevalent mechanism in natural microbial ecosystems that enables direct cell-to-cell DNA transfer, and has the potential to serve as an ecological control method to program long-term coexistence. Thus, inspired by nature, this talk will discuss work in the lab focusing on leveraging plasmid conjugation as an engineering strategy for controlling microbial community composition and stability. Specifically, to explore how HGT can be applied as a control strategy for community composition, we first developed a kinetic model of conjugation dynamics in a two-species system, incorporating key parameters dictating plasmid conjugation dynamics, to determine the landscape of plasmid-mediated species control. Analytical derivations with numerical simulations revealed parameter regimes where conjugation promotes species coexistence, even in cases where one species would otherwise outcompete the other. Guided by these predictions, experiments using both natural and engineered plasmids confirmed the ability of conjugation to modulate species fractions in a highly predictable and tunable manner. Moreover, they revealed that species interactions and plasmid parameters together define the coexistence regime, which can be optimized to achieve desired community compositions.
Our findings demonstrate that conjugative plasmids significantly enhance population stability across a broad range of conditions compared to non-conjugative systems. This work provides mechanistic insights into the role of HGT in microbial consortia composition and offers a predictive framework for engineering stable microbial communities. Ongoing efforts are focused on extending these principles to applications in bioremediation, bioprocessing, and biomedical engineering.