Context

Commensal bacteria bring to their hosts beneficial effects resulting from the properties of the substances they secrete and the way they interact with other microorganisms of the host. Therefore, they are increasingly used for bacteriotherapy, as exemplified by probiotics administered to re-equilibrate the gut microbiome. For external organs such as skin and mucous tissues, a safe therapeutic strategy requires to prevent the uncontrolled proliferation of bacteria applied to the organ, in order to maintain an equilibrated microbiome and avoid nefarious penetration in the body through possible scratches and cuts. This can be realized by entrapping bacteria in micro-compartments that are only porous to secreted substances (and nutrients), while allowing bacteria to proliferate at a very low rate in a metabolically-active state, for a reasonably length of time from the onset of their application on the organ.

However, such applications raise basic issues, which can broadly be gathered under the general question of how life, proliferation, secretion, and ultimately death of bacteria, can be controlled or activated by interfering with bacteria regulatory networks via their compartmentalization and the fine tuning of their environment. For this, we propose to combine the genetic modification of bacteria to rewire their secretion pathways, with the spatio-temporal control of their activity by encapsulation in micro-structured circuits made of compartments connected in a designed architecture. More precisely, we will explore the combination of cell-cell communication between human commensal bacteria, and of their compartmentalization in properly-designed circuits of compartments to (1) activate on-demand specific regulatory networks leading to the production of beneficial molecules acting on pathogens (bacteriocins) and (2) to maintain this secretory activity and bacterial life for long times. Our long-term application perspective is to use this strategy to fabricate a super-secreting bacterial device acting against pathogens for long times.