Modeling the overproduction of ribosomes when antibacterial drugs act on cells

Abstract

Bacteria that are subjected to ribosome inhibiting antibiotic drugs show an interesting behavior: Although the drug slows down cell growth, it also paradoxically increases the cells concentration of ribosomes. We combine a prior nonlinear model of the energy-biomass balance in undrugged E. coli cells (Maitra and Dill, PNAS 2015) with Michaelis-Menten binding of drugs that inactivate ribosomes. Predictions are in good agreement with experiments on ribosomal concentrations and synthesis rates vs. drug concentrations and growth rates. The model indicates that added drug drives the cell to overproduce ribosomes keeping roughly constant the level of ribosomes producing ribosomal proteins, an important quantity for cell growth. The model also predicts that ribosomal production rates should increase, then decrease with added drug. This model gives insights into cellular driving forces and suggests new experiments.