Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study
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Updated: Aug 31, 2025
Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
Published on: September 11, 2020
Stephanie W Lo1, Kate Mellor1, Robert Cohen2
1Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
Background:
Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods:
Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590).
Findings:
Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain.
Interpretation:
Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases.
Funding:
Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.
Insights
Emerging serotype 24F, driven by the multidrug-resistant GPSC10 lineage, poses a challenge to current pneumococcal conjugate vaccines (PCV). Further investigation into such lineages is crucial for next-generation vaccine strategies.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Serotype 24F is an emerging Streptococcus pneumoniae serotype following the introduction of pneumococcal conjugate vaccines (PCV).
- Understanding the genetic lineages driving serotype 24F expansion is critical for public health.
- This study investigates the global epidemiology of serotype 24F.
Purpose of the Study:
- To identify the specific pneumococcal lineages responsible for the rise of serotype 24F in France.
- To analyze the global distribution and evolutionary dynamics of these lineages.
- To assess the implications for current and future pneumococcal vaccine strategies.
Main Methods:
- Whole-genome sequencing of serotype 24F isolates from France (2003-2018).
- Analysis of isolates from asymptomatic colonization and invasive disease in individuals under 18.
- Phylogenetic, evolutionary, and spatiotemporal analyses incorporating global data from the Global Pneumococcal Sequencing (GPS) project.
Main Results:
- Three main lineages (GPSC10, GPSC16, GPSC206) drive the global spread of serotype 24F.
- GPSC10, a multidrug-resistant lineage, is the primary driver of 24F increase in France and exhibits high invasive potential.
- GPSC10-24F demonstrated long-range international transmission and rapid spread within France, with a notable shift from serotype 19A in Spain post-PCV13 introduction.
Conclusions:
- The GPSC10 lineage represents a significant challenge for serotype-based pneumococcal vaccine strategies.
- Systematic identification of emerging lineages like GPSC10 is essential for improving next-generation preventive measures against pneumococcal diseases.
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