Comparative Genome Analysis of Extended-Spectrum-β-Lactamase-Producing Sequence Type 131 Strains from Nepal and Japan.

The global spread of extended-spectrum-β-lactamase (ESBL)-producing (ESBL-) has largely been driven by the pandemic sequence type 131 (ST131). This study aimed to determine the molecular epidemiology of their spread in two Asian countries with contrasting prevalence. We conducted whole-genome sequencing (WGS) of ESBL- ST131 strains collected prospectively from Nepal and Japan, two countries in Asia with a high and low prevalence of ESBL-, respectively. We also systematically compared these genomes with those reported from other regions using publicly available WGS data for ST131 strains. Further, we conducted phylogenetic analysis of these isolates and all genome sequence data for ST131 strains to determine sequence diversity. One hundred five unique ESBL- isolates from Nepal (February 2013 to July 2013) and 76 isolates from Japan (October 2013 to September 2014) were included. Of these isolates, 54 (51%) isolates from Nepal and 11 (14%) isolates from Japan were identified as ST131 by WGS. Phylogenetic analysis based on WGS suggested that the majority of ESBL- ST131 isolates from Nepal clustered together, whereas those from Japan were more diverse. Half of the ESBL- ST131 isolates from Japan belonged to virotype C, whereas half of the isolates from Nepal belonged to a virotype other than virotype A, B, C, D, or E (A/B/C/D/E). The dominant sublineage of ST131 was 30Rx, which was most prominent in ESBL- ST131 isolates from Nepal. Our results revealed distinct phylogenetic characteristics of ESBL- ST131 spread in the two geographical areas of Asia, indicating the involvement of multiple factors in its local spread in each region. The global spread of ESBL- has been driven in large part by pandemic sequence type 131 (ST131). A recent study suggested that, within ST131, certain sublineages have disseminated worldwide with little association with their geographical origin, highlighting the complexity of the epidemiology of this pandemic clone. ST131 bacteria have also been classified into four virotypes based on the distribution of certain virulence genes. Information on virotype distribution in Asian ST131 strains is limited. We conducted whole-genome sequencing of ESBL- ST131 strains collected in Nepal and Japan, two Asian countries with a high and low prevalence of ESBL-, respectively. We systematically compared these ST131 genomes with those reported from other regions to gain insights into the molecular epidemiology of their spread and found the distinct phylogenetic characteristics of the spread of ESBL- ST131 in these two geographical areas of Asia.