Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with Escherichia coli

Abstract

Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely related Escherichia coli strains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance.

Phylum barrier and Escherichia coli intra-species phylogeny drive the acquisition of antibiotic-resistance genes

“…Interestingly, a similar role of the genetic background influencing the genomic basis of antibiotic resistance by channelling evolution along different mutational paths has been reported following a long-term in vitro evolution experiment with E. coli [49].…”

“…Such a functional redundancy suggests that the E. coli phylogroups were exposed to the same antibiotic pressure but acquired different ARGs to cope with it in an adaptive convergence process. Interestingly, a similar role of the genetic background influencing the genomic basis of antibiotic resistance by channelling evolution along different mutational paths has been reported following a long-term in vitro evolution experiment with E. coli [ 49 ].…”

Development of antibiotic resistance reveals diverse evolutionary pathways to face the complex and dynamic environment of a long-term treated patient

“…Laboratory-based experimental evolution experiments have been extensively used to replicate bacterial adaptation during antibiotic therapy (MacLean et al, 2010; Palmer and Kishony, 2013; Cabot et al, 2014; Baym et al, 2016; Card et al, 2019; Windels et al, 2020; Card et al, 2021). This approach reduces complexity in order to establish reproducible and well-controlled conditions, from which evolutionary changes and mutational trajectories can be analyzed.…”

“…Our current knowledge regarding the evolution of bacterial antibiotic resistance mainly comes from clinical, microbiological and biochemical studies that are performed under highly controlled conditions (Elena and Lenski, 2003; Weinreich et al, 2006; MacLean et al, 2010; Palmer and Kishony, 2013; Baym et al, 2016; Boolchandani et al, 2019; Card et al, 2021). Collectively, we have learned that the emergence and evolution of antibiotic resistance, one of the greatest challenges to our civilization, is a far more complex phenomenon; few studies exist that offer insights into “real-world” scenarios that adequately or completely explain evolutionary trajectories that shape existing phenotypes (Bershtein et al, 2006; Meini et al, 2015; Stiffler et al, 2015; Prickett et al, 2017; Frimodt-Møller et al, 2018; Andersson et al, 2020; Mehlhoff et al, 2020).…”

Plasmon-Enhanced Antibacterial Activity of Chiral Gold Nanoparticles and In Vivo Therapeutic Effect

“…Furthermore, urinary tract infections may lead to some serious diseases that span from the gastrointestinal tract to extraintestinal sites such as the blood stream and central nervous system, which can be life-threatening [ 7 , 8 ]. Antibiotic treatment is currently the most effective method, but it is easy to promote the emergence of multi-drug resistant E. coli , which constitutes one of the dominant challenges to human health [ 9 , 10 , 11 ]. Additionally, the obvious and continuous decrease in the number of approved antibiotics in the past 10 years has exacerbated the increasingly threatening circumstances [ 12 , 13 ].…”