@article {Maitra024703, author = {Arijit Maitra and Ken A. Dill}, title = {Modeling the overproduction of ribosomes when antibacterial drugs act on cells}, elocation-id = {024703}, year = {2015}, doi = {10.1101/024703}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Bacteria that are subjected to ribosome inhibiting antibiotic drugs show an interesting behavior: although adding drugs slows down cell growth, it also paradoxically increases the cell{\textquoteright}s concentration of ribosomes. We combine a prior nonlinear model of the energy-biomass balance in undrugged 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 the cell overproduces ribosomes in order to maintain an essentially constant ratio of active ribosomes to nonribosomal proteins, a key controller of cell behavior. The model also shows that drugged cells tend to maintain patterns of energy influx rates (glucose {\textrightarrow} ATP) that are the same as when the cells are undrugged. And, it predicts that adding drugs to slow-growing cells leads to a maximum point in the rate of ribosome synthesis. This type of modeling can provide insights into cellular driving forces that are difficult to measure.}, URL = {https://www.biorxiv.org/content/early/2015/08/14/024703}, eprint = {https://www.biorxiv.org/content/early/2015/08/14/024703.full.pdf}, journal = {bioRxiv} }