Genomic global epidemiology and evolution of Escherichia coli ST131 clade A

During the 2010s, Escherichia coli ST131 clade A tested sensitive to most antibiotics. In the 2020s, Europe experienced outbreaks of fluoroquinolone-resistant ST131-A that contained CTX-M β-lactamases and OXA-48-like carbapenemases. We investigated the acquisition of different antimicrobial resistance determinants in the emergence of multidrug-resistant (MDR) ST131-A. Phylogenetic analysis and Bayesian inference were utilized to define subclades and clusters (within subclades) and investigate the evolutionary history of ST131-A, using sequenced genomes and publicly available genomic data (n=2,905). ST131-A consisted of five dominant subclades and ten frequent clusters, representing 93 and 83% of the total population, respectively. The sampled most recent common ancestors of the dominant subclades dated mainly to the 1990s. Several MDR clusters linked with diverse quinolone resistance-determining region mutations, CTX-M and OXA-48-like genes diversified during the 2000s. The distribution and mobile genetic elements linked with bla _CTX-M-14, bla _CTX-M-15 and bla _CTX-M-27 differed among ST131-A subclades and clusters across geographic locations. Three ST131-A clusters belonging to different subclades and carrying bla _OXA-48 and bla _OXA-244 in distinct genetic contexts were associated with the recent European dissemination. The identification of MDR ST131-A subclades and clusters with divergent molecular architectures emerging independently across regions highlights the challenges for public health surveillance and control efforts.