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

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 b-lactam drugs (Santos-Lopez et al. 2019). Here we study how this prior history influences subsequent evolution in new b-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.

Evolutionary History and Strength of Selection Determine the Rate of Antibiotic Resistance Adaptation

“…Experimental evolution has been an essential tool to address these questions and to unravel the interaction between selection, chance, and historical contingency in microbial populations ( Weinreich et al 2006 ; Jansen et al 2013 ; Blount et al 2018 ; Roemhild et al 2018 ; Santos-Lopez et al 2021 ). By combining experimental microbiology with whole-genome sequencing, previous studies have been able to follow evolutionary trajectories towards resistance and studied the accumulation of mutations in different ecological contexts.…”

“…Other studies have shown that, as selection increases, the benefit associated with drug-resistance mutations is enhanced, thus increasing mutant frequency in the population and reducing overall genetic diversity. Consequently, strong selective pressures often display similar phenotypic trajectories towards resistance ( Toprak et al 2012 ) and are known to mitigate the effect of historical contingencies ( Pennings 2012 ; Santos-Lopez et al 2021 ). Population bottlenecks are also major determinants of the repeatability of adaptation as they affect genetic drift ( De Visser and Krug 2014 ).…”

Historical Contingency Drives Compensatory Evolution and Rare Reversal of Phage Resistance

“…Notably, the effect we observed was strong when the phage selection event was recent but was no longer detectable after populations had spent an extended period of time in the same environment. Thus, recent historical differences appear to be more important than distant historical differences in shaping subsequent evolution ( Travisano et al 1995 ; Yen and Papin 2017 ; Santos-Lopez et al 2021 ).…”

Modeling Polygenic Antibiotic Resistance Evolution in Biofilms

“…It is now widely accepted that multiple genes of various effects determine antibiotic resistance in planktonic bacteria (Petchiappan and Chatterji, 2017;Apjok et al, 2019;Igler et al, 2021). Similarly, multiple mutations were recently implicated in biofilm recalcitrance (Santos-Lopez et al, 2019;Santos-Lopez and Cooper, 2021). Evolutionary experiments have shown that when biofilm and planktonic bacteria are exposed to increasing concentrations of antibiotics, the biofilm populations harbor even higher genetic diversity than planktonic populations that experienced the same treatment (Ahmed et al, 2018(Ahmed et al, , 2020Santos-Lopez et al, 2019;Santos-Lopez and Cooper, 2021).…”