Plasmid-mediated acquisition and chromosomal integration of in a subclade of ST131-30 clade C1.

ST131 is a multidrug-resistant lineage associated with the global spread of extended-spectrum β-lactamase-producing organisms. Particularly, ST131 clade C1 is the most predominant clade in Japan, harboring at a high frequency. However, the process of resistance gene acquisition and spread remains unclear. Here, we performed whole-genome sequencing of 19 strains belonging to 12 STs and 12 types collected between 1997 and 2016. Additionally, we analyzed the full-length genome sequences of 96 ST131-30 clade C0 and C1 strains, including those obtained from this study and those registered in public databases, to understand how ST131 clade C1 acquired and spread . We detected conjugative IncFII plasmids and IncB/O/K/Z plasmids carrying in diverse genetic lineages of strains from the 1990s to the 2010s, suggesting that these plasmids played an important role in the spread of . Molecular phylogenetic and molecular clock analyses of the 96 ST131-30 clade C0 and C1 strains identified 8 subclades. Strains harboring were clustered in subclades 4 and 5, and it was inferred that clade C1 acquired around 1993. All 34 strains belonging to subclade 5 possessed with IS upstream at the same chromosomal position, indicating their common ancestor acquired in a single IS-mediated transposition event during the early formation of the subclade around 1999. Therefore, both the horizontal transfer of plasmids carrying to diverse genetic lineages and chromosomal integration in the predominant genetic lineage have contributed to the spread of .