Predicting the evolution of antibiotic resistance

Abstract

Predicting the evolution of antibiotic resistance is critical for realizing precision antibiotic therapies. How exactly to achieve such predictions is a theoretical challenge. Insights from mathematical models that reflect future behavior of microbes under antibiotic stress can inform intervention protocols. However, this requires going beyond heuristic approaches by modeling ecological and evolutionary responses linked to metabolic pathways and cellular functions. Developing such models is now becoming possible due to increasing data availability from systematic experiments with microbial systems. Here, I review recent theoretical advances promising building blocks to piece together a predictive theory of antibiotic resistance evolution. I focus on the conceptual framework of eco-evolutionary response models grounded on quantitative laws of bacterial physiology. These forward-looking models can predict previously unknown behavior of bacteria upon antibiotic exposure. With current developments covering mostly the case of ribosome-targeting antibiotics, I write this Opinion piece as an invitation to generalize the principles discussed here to a broader range of drugs and context dependencies.