The roles of history, chance, and natural selection in the evolution of antibiotic resistance

eLife

Alfonso Santos-Lopez¹  Allison L Haas¹  Caroline Turner¹  Christopher W Marshall¹  Vaughn S Cooper²  Javier Rasero³ 

[1] Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, United States;Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, United States;Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, United States;Department of Psychology, Carnegie Mellon University, Pittsburgh, United States;

关键词: acinetobacter;    collateral sensitivity;    population genetics;    genomics;    efflux;    None;   

DOI  :  10.7554/eLife.70676

来源: eLife Sciences Publications, Ltd

【 摘 要 】

History, chance, and selection are the fundamental factors that drive and constrain evolution. We designed evolution experiments to disentangle and quantify effects of these forces on the evolution of antibiotic resistance. Previously, we showed that selection of the pathogen Acinetobacter baumannii in both structured and unstructured environments containing the antibiotic ciprofloxacin produced distinct genotypes and phenotypes, with lower resistance in biofilms as well as collateral sensitivity to β-lactam drugs (Santos-Lopez et al., 2019). Here we study how this prior history influences subsequent evolution in new β-lactam antibiotics. Selection was imposed by increasing concentrations of ceftazidime and imipenem and chance differences arose as random mutations among replicate populations. The effects of history were reduced by increasingly strong selection in new drugs, but not erased, at times revealing important contingencies. A history of selection in structured environments constrained resistance to new drugs and led to frequent loss of resistance to the initial drug by genetic reversions and not compensatory mutations. This research demonstrates that despite strong selective pressures of antibiotics leading to genetic parallelism, history can etch potential vulnerabilities to orthogonal drugs.

【 授权许可】

CC BY