Coupling spatial segregation with synthetic circuits to control bacterial survival.

Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial swarmbot, which employs spatial arrangement to control the growth dynamics of engineered bacteria. As a proof of principle, we demonstrated a safeguard strategy to prevent unintended bacterial proliferation. In particular, we adopted several synthetic gene circuits to program collective survival in Escherichia coli: the engineered bacteria could only survive when present at sufficiently high population densities. When encapsulated by permeable membranes, these bacteria can sense the local environment and respond accordingly. The cells inside the microbial swarmbot capsules will survive due to their high densities. Those escaping from a capsule, however, will be killed due to a decrease in their densities. We demonstrate that this design concept is modular and readily generalizable. Our work lays the foundation for engineering integrated and programmable control of hybrid biological-material systems for diverse applications.

A power-law dependence of bacterial invasion on mammalian host receptors.

Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host ß1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.

Programmed cell death in bacteria and implications for antibiotic therapy.

It is now well appreciated that programmed cell death (PCD) plays critical roles in the life cycle of diverse bacterial species. It is an apparently paradoxical behavior as it does not benefit the cells undergoing PCD. However, growing evidence suggests that PCD can be 'altruistic': the dead cells may directly or indirectly benefit survivors through generation of public goods. This property provides a potential explanation on how PCD can evolve as an extreme form of cooperation, although many questions remain to be addressed. From another perspective, as PCD plays a critical role in bacterial pathogenesis, it has been proposed as a potential target for new antibacterial therapy. To this end, understanding the population and evolutionary dynamics resulting from PCD and public goods production may be a key to the success of designing effective antibiotic treatment.