Negative feedback increases information transmission, enabling bacteria to discriminate sublethal antibiotic concentrations

In the cell, noise constrains information transmission through signaling pathways and regulatory networks. There is growing evidence that the channel capacity of cellular pathways is limited to a few bits, questioning whether cells quantify external stimuli or rely on threshold detection and binary on/off decisions. Here, using fluorescence microscopy and information theory, we analyzed the ability of the transcriptional regulator TetR to sense and quantify the antibiotic tetracycline. The results showed that noise filtering by negative feedback increased information transmission up to 2 bits, generating a graded response able to discriminate different antibiotic concentrations. This response matched the antibiotic subinhibitory selection window, suggesting that information transmission through TetR is optimized to quantify sublethal antibiotic levels. Noise filtering by negative feedback may thus boost the discriminative power of cellular sensors, enabling signal quantification.