Phylogenetic analysis of serotype 19A-sequence type (ST)2331 Streptococcus pneumoniae associated with the Pneumococcal Molecular Epidemiology Network (PMEN)34 clone predominant in Japan after the introduction of the 7-valent pneumococcal conjugate va

Following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), serotype 19A Streptococcus pneumoniae emerged as a major cause of paediatric pneumococcal disease in Japan. Unlike global trends, in which multidrug-resistant serotype 19A-sequence type (ST)320 predominated, serotype 19A-ST2331 became one of the dominant lineages in Japan. The evolutionary origins of serotype 19A-ST2331 and the reasons for its domestic success remain unclear. To investigate the evolutionary origin and dissemination of the serotype 19A-ST2331 lineage, we analysed whole-genome sequences of 42 clonal complex (CC)2331 isolates collected in Japan between 2004 and 2017 and compared them with 825 genetically related global isolates. Phylogenetic analysis showed that Japanese serotype 19A-ST2331 isolates formed a distinct Japan-associated cluster within Global Pneumococcal Sequence Cluster 32 that was closely related to the globally disseminated Pneumococcal Molecular Epidemiology Network (PMEN)34 clone, typically represented by serotype 12F-ST218. Among the 42 Japanese CC2331 isolates, 40 were serotype 19A, whereas only two non-19A isolates were identified. Serotype 19A was absent from the 825 non-Japanese isolates, indicating that serotype 19A-ST2331 represents a globally rare, Japan-specific lineage. Most Japanese isolates remained susceptible to β-lactams, whereas 83.3% were erythromycin-resistant and carried either mefA/E or ermB . A highly clonal mefA/E -positive subclade was dated to a most recent common ancestor at ∼1998.5. These findings indicate that serotype 19A-ST2331 emerged before 2000 from an ST218-related ancestor through serotype switching and subsequently underwent local expansion in Japan. Although the ancestral intermediate was not represented in the present collection, the successful establishment of this clone may have been facilitated by the combined selective advantages conferred by the serotype 19A capsule and macrolide resistance in the post-PCV7 setting in Japan.