David Helekal, Tatum D Mortimer, Aditi Mukherjee, Gabriella Gentile, Adriana Le Van, Robert A Nicholas, Ann E Jerse, Samantha G Palace, Yonatan H Grad
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Quantifying the impact of antibiotic use and genetic determinants of resistance on bacterial lineage dynamics.
The dynamics of antimicrobial resistance in bacterial populations are informed by the fitness impact of genetic determinants of resistance and antibiotic pressure. However, estimates of real-world fitness impact have been lacking. To address this gap, we developed a hierarchical Bayesian phylodynamic model to quantify contributions of resistance determinants to strain success in a 20-year collection of Neisseria gonorrhoeae isolates. Fitness contributions varied with antibiotic use, and genetic pathways to phenotypically identical resistance conferred distinct fitness effects. These findings were supported by in vitro and experimental infection competition. Quantifying these fitness contributions to lineage dynamics reveals opportunities for investigation into other genetic and environmental drivers of fitness. This work thus establishes a method for linking pathogen genomics and antibiotic use to define factors shaping ecological trends.
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