Bistable Bacterial Growth Dynamics in the Presence of Antimicrobial Agents

The outcome of an antibiotic treatment on the growth capacity of bacteria is largely dependent on the initial population size (Inoculum Effect). We characterized and built a model of this effect in E. coli cultures using a large variety of antimicrobials, including conventional antibiotics, and for the first time, cationic antimicrobial peptides (CAMPs). Our results show that all classes of antimicrobial drugs induce an inoculum effect, which, as we explain, implies that the dynamic is bistable: For a range of anti-microbial densities, a very small inoculum decays whereas a larger inoculum grows, and the threshold inoculum depends on the drug concentration. We characterized three distinct classes of drug-induced bistable growth dynamics and demonstrate that in rich medium, CAMPs correspond to the simplest class, bacteriostatic antibiotics to the second class, and all other traditional antibiotics to the third, more complex class. These findings provide a unifying universal framework for describing the dynamics of the inoculum effect induced by antimicrobials with inherently different killing mechanisms.