Predicting Antibiotic Effectiveness Across the Range of Bacterial Diversity

How antibiotic efficacy varies with bacterial species is of basic and applied importance, including understanding of microbial dynamics in clinical and ecological contexts. Cellular components that antibiotics target — DNA, proteins, mRNA, tRNA, cellular envelope, and ribosomes — all scale non-linearly with cell volume. We develop theory that shows how antibiotic efficacy may depend on cell size based on the specific cellular components targeted by the antibiotics and the nonlinearities between those components and cell size. We measure cell size and minimum inhibitory concentrations in 11 bacterial species and 24 antibiotics. We present a detailed model for ribosome-targeting antibiotics through which we can generate dose-response curves and make predictions for minimum inhibitory concentrations based on cell size. We find that energetic and volumetric limitations on cell growth create trade-offs, leading to the surprising prediction that mid-sized cells are the least susceptible to antibiotics. This finding is matched by our theoretical predictions