Genomic epidemiology of Streptococcus pneumoniae GPSC6: post-vaccine expansion of β-lactam-susceptible serotype 24F in Europe

Streptococcus pneumoniae serotype 24F has emerged as a major cause of invasive pneumococcal disease in Europe following the introduction of PCV13 yet remains absent from current paediatric vaccine formulations. We investigated the genomic epidemiology and phylodynamics of serotype 24F within Norway by focusing on the dominant strain Global Pneumococcal Sequence Cluster 6 (GPSC6) and placed these isolates in a global context using 972 genomes from 29 countries. GPSC6 is composed of distinct lineages, which we estimate to have diverged around the mid-twentieth century. Before the pneumococcal conjugate vaccine (PCV) era, Lineage 1 was composed predominantly of vaccine serotypes. The past success of Lineage 1 likely came from its antimicrobial resistance (AMR) gained in the 1980s. Since the introduction of PCVs in childhood immunization programmes, Lineage 2 has expanded rapidly, driven by clades with serotypes not covered by the PCVs. A time-calibrated phylogeny indicates that GPSC6-24F originated in the 1980s and expanded rapidly after the introduction of PCV7 in 2006. In Norway, two importations in the period 2007–2009 seeded most local transmissions. The effective population size of GPSC6 declined after PCV7 introduction, followed by expansion of non-vaccine serotypes, notably 24F and 11A. In silico AMR profiling revealed that GPSC6-24F isolates likely remain susceptible to β -lactams and other antimicrobial classes but are resistant to co-trimoxazole, contrasting the expansion of multidrug-resistant GPSC10-24F reported from high-antibiotic-use settings. Vaccine-driven selection rather than AMR seems to be shaping the GPSC6-24F dynamics in Europe and highlights the need for continued genomic surveillance, as 24F is not covered by paediatric PCV formulations.