Abstract
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.
Highlights
Evolution can be propelled by natural selection, it can wander with the chance effects of mutation and genetic drift, and it can be constrained by history, whereby past events limit or even potentiate the future [1,2,3,4,5]
(21), we propagated a single clone of A. baumannii for 12 days in increasing concentrations of the fluoroquinolone antibiotic ciprofloxacin (CIP)
The evolution and spread of antimicrobial resistance (AMR) provide a test of this hypothesis, because countless evolution experiments are initiated each day with each new prescription to combat infections caused by bacteria with different histories
Summary
Evolution can be propelled by natural selection, it can wander with the chance effects of mutation and genetic drift, and it can be constrained by history, whereby past events limit or even potentiate the future [1,2,3,4,5]. In the absence of chance and history, selection will cause the most fit genotype to fix in the particular environment, and provided this variant is available, evolution will be perfectly predictable [7, 9]. Historical and stochastic processes inevitably produce some degree of contingency, making evolution less predictable, reflecting the importance of evolutionary history [3, 6, 10, 11]. The evolution of a new trait, whether by horizontally acquired genes or de novo mutation, is a stochastic process that depends on available genetic variation capable of producing a new trait [12, 13]
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