1. Microbial consortia are difficult to study All associations are different; Many specific mechanisms (antibiotics, physical barriers etc); No reliable “observables”; Generic (simplified) models: 1) synthetic communities (wet lab) 2) agent-based models (in silico)

2. Observed growth patterns No (very slow) growth Swarming (fast, diffusion limited growth) Constrained growth Lab experiment

3. Biological model: Quorum sensing QUORUM SENSING Theoretical model

4. Simplified example Signal Protease aa Cell 1 Cell 2 Food “Physicochemical” mechanism: production, diffusion, decay Theoretical model

5. Regulatory model [R-S] Signal S Signal synthase I Sensor R Metabolism Movement 1) Autoinduction, possitive feedback loop S 2) Equilibrium of internal and external signal levels 3) Can be studied with knockout mutants Theoretical model

6. Regulatory model: communication and cooperation [R-S] Signal S Signal synthase I Sensor R Metabolism Movement Signal = communication Sensing = cooperation Non-communicating mutant Theoretical model

7. Competition of strains: Cooperation or collapse WT + SN 24 h WT + SB Transient phaseSteady phase WT WT+SN WT+SB (QS collapse) SN or SB alone (no movement) “No swarming” (NS) “Swarming”“Collapse” (C) Phenotypes:

8. B P. aeruginosa B. cepacia P.aeruginosa + B. cepacia A BC 1 WT+BC 2 97:3 Cooperation combines the skills of participants Divided plate experiment: Center:Rim: PA: + - BC: - +

9. Collapse of a dendritic community Ádám Kerényi Blue: WT co-operators Red: non-cooperating cheats Computatonal model

10. B) 16 hours after SB injection A) Before SB injection = places of SB injection C) Escaping dendrite magnified Collapse is local: it protects against bad mutations.... Communication is not global.... Iris Bertani Lab experiment

11. Globally communicating community (e.g. well-mixed, liquid media) Locally communicating microcommunities (e.g. swarming, growth on surfaces) Local collapse, local communication vulnerable stable Dóra Bihary Polymicrobial communities are less efficient but more versatile than (some) monocultures…

12. Summary Microbial communities were modeled with engineered bacteria and computer models. Non-communicating mutants can be part of the community, non- cooperating mutants cause (local) collapse. Microbial communities are stable because: –Cooperation combines the skills of participants. –Deleterious mutants are eliminated by local collapse Stability is a general consequence of local communication, it acts in absence of specific mechanisms… Polymicrobial communities are less efficient but more versatile than (some) monocultural communities…