To Örebro University

Modern medicine relies heavily on effective antimicrobial therapies. However, rapid emergence and global spread of antimicrobial resistance (AMR) threaten the treatment and control of bacterial infections. Neisseria gonorrhoeae, the causative agent of gonorrhoea, has an extraordinary capacity to acquire and develop resistance to all antimicrobials introduced for treatment. The aim of this study was to gain insight into the evolution and global emergence of AMR over the past century. This thesis further investigates whether the observed genomic data patterns are sufficiently informative for accurate prediction of antimicrobial susceptibility that can directly inform treatment.

By applying whole-genome sequencing (WGS) to global, historical, and contemporary gonococcal collections spanning all continents and isolated from the pre-antibiotic era to the present day, several questions can be addressed. The data revealed that the global gonococcal population is divided into two distinct lineages with different evolutionary strategies. Furthermore, temporal analysis demonstrates that the modern N. gonorrhoeae is younger than previously presumed and that antimicrobial exposure has been a major driver of the evolution of this species.

The accumulated knowledge base of phenotypic and especially genomic AMR generated in this work is compiled and integrated within a dedicated analytical framework, SensiTyper, demonstrating that WGS-based approaches can infer antimicrobial susceptibility and recommend susceptibility-guided individualised treatment strategies.