Growth rate controls the sensitivity of gene regulatory circuits

Microbes adapt to their environments using gene regulatory switches that sense environmental signals and induce target genes in response. Mathematical modeling predicts that, because growth rate sets the intracellular dilution rate, the sensitivity of regulatory switches to chemical cues systematically decreases with growth rate. We experimentally validate that the concentration of inducer required to activate <i>E. coli</i>'s <i>lac</i> operon increases quadratically with growth rate when varying nutrients but is invariant when varying growth rate through translation inhibition. We further establish that this growth-coupled sensitivity (GCS) allows bacteria to implement concentration-dependent sugar preferences, in which a new carbon source is used only if its concentration is sufficient to improve upon the current growth rate. Using microfluidics in combination with time-lapse microscopy, we validate this prediction at the single-cell level using mixtures of glucose and lactose. Overall, GCS causes cells to automatically become more sensitive to environmental signals when their growth rate decreases.