# Quantifying the real-world impact of antibiotic use and genetic determinants of resistance on gonococcal dynamics

## TL;DR

This study uses a new model to show how antibiotic use and genetic changes affect the spread of antibiotic-resistant gonorrhea bacteria.

## Contribution

A novel hierarchical Bayesian phylodynamic model is developed to quantify real-world fitness impacts of resistance determinants and antibiotic use.

## Key findings

- Fitness contributions of resistance determinants varied with antibiotic use over 20 years.
- Genetic pathways leading to the same resistance phenotype had distinct fitness effects.
- In vitro and mouse experiments validated the model's findings on lineage dynamics.

## Abstract

The dynamics of antimicrobial resistance in bacterial populations are influenced 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, which over this period included ciprofloxacin, cefixime, ceftriaxone and azithromycin, and genetic pathways to phenotypically identical resistance conferred distinct fitness effects. These findings were supported by competition experiments both in vitro and in the mouse model of gonococcal infection. 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.

Phylodynamic modelling shows how the changing antibiotic landscape and genetic determinants of resistance shape real-world gonococcal dynamics. Experiments validated that determinants with identical resistance phenotype differed in impact on fitness.