Fig. S1 Cytoplasm V c Periplasm V pp Microenvironment V e D pp AiAi A pp AeAe k IMOM * * * D.

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Fig. S1 Cytoplasm V c Periplasm V pp Microenvironment V e D pp AiAi A pp AeAe k IMOM * * * D

A Type IIa Type Ia AiAi k AeAe D VcVc dada dada * VeVe * B k D VcVc dada dada * VeVe * AiAi AeAe D imp Fig. S2

Percent effector activation Basal Induction level Fig. S V e /V c

E nM hr -1 0 Shutoff Induction E opt OFF R S Q E max P Fig. S4 V e /V c

E opt E max Cost Benefit f max Activation E Cost or Benefit Fig. S5

A B v Low Benefit v opt = Cell density n T cells/ml × Cell density n T cells/ml High Benefit v opt = inf v Fig. S6

Ab e P Ab i Sensor E VeVe P + * Fig. S7

C OFF ON v d a hr Type I Type II Fig. S8

Fig. S9 AiAi k AiAi k AiAi k AeAe D V V B D D S P N + sensor S P N + S P N + A

Log 10 ( v ) v calculated v observed Log 10 ( v ) v calculated v observed Fig. S10 A B

Log 10 ( v calculated ) Log 10 ( v observed ) sin CSF1 cin lux rhl las tra CSF2 luxS car ain HAI1 agr comX CAI-1 CSP* CSP luxS* Fig. S11 cep