Abstract
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.