Phylogenomics, evolution and origin of multidrug-resistant ST15.

We studied the genomic evolution and transmission dynamics of multidrug-resistant ST15 (Institut Pasteur scheme) , examining resistance gene acquisition, clonal diversification, geographic distribution and origin of this high-risk clone. One hundred and fifty-two (=152) ST15 genomes from 18 countries (1997-2024), including 42 isolates from U.S. Military Treatment Facilities and 110 publicly available genomes in GenBank, were analysed. Whole-genome sequencing, assembly and annotation were performed using established bioinformatics pipelines. Phylogenetic analysis based on core-genome SNPs - filtered for recombination with - was combined with mobile element and resistance gene identification. ST15 isolates separated into two main clades with distinct subclades and variable resistance profiles. Homologous recombination drove the diversification of resistance determinants, including multiple alleles. Key resistance genes, such as , were disseminated via known transposons (Tn or Tn), while plasmid exchange, including module acquisitions, also played a role in the spread of . Patristic analysis identified Argentina as the likely origin for the emergence of ST15, aligning with early 1997 isolates. Recombination, transposon-mediated gene transfer and plasmid exchange have been central in driving the evolution and global dissemination of ST15.