气候变化领域集成服务门户(CCPortal): Metabolic fitness landscapes predict the evolution of antibiotic resistance

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DOI	10.1038/s41559-021-01397-0
	Metabolic fitness landscapes predict the evolution of antibiotic resistance
	Pinheiro F.; Warsi O.; Andersson D.I.; L?ssig M.
发表日期	2021
ISSN	2397-334X
起始页码	677
结束页码	687
卷号	5 期号:5
英文摘要	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. The model maps 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 growth rates and resistance levels, which characterize Pareto resistance mutations emerging at different drug dosages. We also predict the prevalent resistance mechanism depending on drug and nutrient levels: low-dosage drug defence is mounted by regulation, evolution of distinct metabolic sectors sets in at successive threshold dosages. Evolutionary resistance mechanisms include membrane permeability changes and drug target mutations. These predictions are confirmed by empirical growth inhibition curves and genomic data of Escherichia coli populations. Our results show that resistance evolution, by coupling major metabolic pathways, is strongly intertwined with systems biology and ecology of microbial populations. ? 2021, The Author(s), under exclusive licence to Springer Nature Limited.
语种	英语
scopus关键词	antiinfective agent; Escherichia coli protein; antibiotic resistance; Escherichia coli; genetics; mutation; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Mutation
来源期刊	Nature Ecology & Evolution
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/256957
作者单位	Institute for Biological Physics, University of Cologne, Cologne, Germany; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
推荐引用方式 GB/T 7714	Pinheiro F.,Warsi O.,Andersson D.I.,et al. Metabolic fitness landscapes predict the evolution of antibiotic resistance[J],2021,5(5).
APA	Pinheiro F.,Warsi O.,Andersson D.I.,&L?ssig M..(2021).Metabolic fitness landscapes predict the evolution of antibiotic resistance.Nature Ecology & Evolution,5(5).
MLA	Pinheiro F.,et al."Metabolic fitness landscapes predict the evolution of antibiotic resistance".Nature Ecology & Evolution 5.5(2021).