Comprehensive genomic analysis of ESBL- and carbapenemase-producing Escherichia coli ST131 in Japan: Genetic characteristics of pandemic clade C.

INTRODUCTION

The global dissemination of extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Escherichia coli sequence type 131 (ST131), particularly clade C, represents a major public health concern. However, the clade-specific genomic features underlying the long-term persistence and international spread of this lineage remain incompletely understood.

METHODS

We performed whole-genome sequencing and comparative genomic analyses of 121 clinical E. coli isolates, including 83 ST131 and 38 non-ST131 strains, collected from 24 healthcare-associated facilities in Japan between 2001 and 2018. Plasmid replicon types, antimicrobial resistance genes, virulence factors, quinolone resistance-determining region (QRDR) mutations, and chromosomal structural variations were analyzed across ST131 clades.

RESULTS

ST131 isolates, particularly clade C, showed a significantly higher prevalence of IncF plasmid replicons, QRDR mutations, and uropathogenic virulence genes such as iha, papA, kpsM, and usp compared with non-ST131 isolates. In contrast, dfrA family genes were less frequent in clade C, suggesting potential retained susceptibility to trimethoprim-sulfamethoxazole. Phylogenetic analysis demonstrated long-term persistence of clade C subclades (C1-nM27, C1-M27, and C2) in Japan. A clade-specific chromosomal region, M27PP1, encoding an ATP-binding protein with a conserved AAA + ATPase domain within a clade-specific genomic island, was identified exclusively in C1-M27 isolates.

CONCLUSIONS

Our findings highlight distinct clade-specific genomic characteristics of ST131 clade C in Japan, particularly in C1-M27. While the biological function of M27PP1 remains to be experimentally determined, its lineage-restricted distribution suggests a potential role in the long-term persistence and dissemination of this subclade. Continued genomic surveillance is essential for understanding and controlling high-risk E. coli lineages.