Predicting trajectories and mechanisms of antibiotic resistance evolution

Autor:	Pinheiro, Fernanda, Warsi, Omar, Andersson, Dan I., Lässig, Michael
Rok vydání:	2020
Předmět:	Quantitative Biology - Populations and Evolution Physics - Biological Physics Quantitative Biology - Cell Behavior
Druh dokumentu:	Working Paper
Popis:	Bacteria evolve resistance to antibiotics by a multitude of mechanisms. A central, yet unsolved question is how resistance evolution affects cell growth at different drug levels. Here we develop a fitness model that predicts growth rates of common resistance mutants from their effects on cell metabolism. We map metabolic effects of resistance mutations in drug-free environments and under drug challenge; the resulting fitness trade-off defines a Pareto surface of resistance evolution. We predict evolutionary trajectories of dosage-dependent growth rates and resistance levels, as well as the prevalent resistance mechanism depending on drug and nutrient levels. These predictions are confirmed by empirical growth curves and genomic data of E. coli populations. Our results show that resistance evolution, by coupling major metabolic pathways, is strongly intertwined with systems biology and ecology of microbial populations. Comment: joint first authors: Fernanda Pinheiro, Omar Warsi; corresponding authors: Dan I. Andersson, Michael L\"assig
Databáze:	arXiv
Externí odkaz:	http://arxiv.org/abs/2007.01245 Zobrazit plný text záznamu View this record from Arxiv