A mismatch between slow protein synthesis and fast environmental fluctuations determines tradeoffs in bacterial...

Microbes live in environments that fluctuate faster than they can adjust their cellular machinery. To survive these fluctuations, they must dynamically regulate protein synthesis-a resource-intensive process that is often slower than environmental changes. Here, we develop a mechanistic model coupling antibiotic kinetics with dynamic proteome allocation to understand how limitations in translational capacity shape acclimation strategies. Using translation-inhibiting antibiotics and resistance proteins, we show that the temporal mismatch between environmental perturbations (seconds) and protein synthesis responses (hours) creates a growth advantage for anticipatory strategies where cells pre-synthesize resistance proteins before antibiotic exposure. Further, we find that the largest benefits of anticipation and the largest protein fractions reserved for anticipation are realized in environments with multiple antibiotics, suggesting that anticipation is most important in complex environments. This work establishes a framework for quantifying the costs and benefits of various acclimation strategies in dynamical environments based on the fundamental constraints of protein synthesis, with implications for microbial ecology, antibiotic resistance, and biotechnology applications.