CC180 clade dynamics do not universally explain Streptococcus pneumoniae serotype 3 persistence post-vaccine: a...

Area of Science:

• Genomics and Molecular Epidemiology
• Vaccine-Preventable Diseases
• Microbial Evolution

Background:

• Clonal complex 180 (CC180) is the predominant clone of serotype 3 Streptococcus pneumoniae (Spn), causing significant global disease burden.
• The 13-valent pneumococcal conjugate vaccine (PCV13) shows limited efficacy against serotype 3 Spn, suggesting potential vaccine escape mechanisms.
• Previous observations in the US, England, and Wales indicated PCV13 may favor resistant clades of CC180, while Spain showed different dynamics.

Purpose of the Study:

• To investigate the population genomics and molecular epidemiology of serotype 3 Spn in Portugal following PCV13 introduction.
• To test the hypothesis that PCV13 drives a population shift favoring vaccine-resistant CC180 clades.
• To compare genomic and epidemiological features of serotype 3 Spn strains in Portugal with global data.

Main Methods:

• Whole-genome sequencing (WGS) of 501 serotype 3 Spn strains from Portugal (1999-2020).
• Phylogenetic analyses, pangenome profiling, and genome-wide association study (GWAS).
• Antibiotic susceptibility testing and comparative genomics with over 2600 global MLST180 WGS datasets.

Main Results:

• CC180 Clades I-VI showed decreased association with invasive disease and adult patients compared to non-invasive pneumonia and pediatric patients, respectively.
• A significant shift in serotype 3 Spn clades was observed post-PCV13, with Clades I-VI comprising the majority of strains; Clade I became dominant (54%) in Portugal.
• Portuguese and Spanish Clade I strains, while largely antibiotic-sensitive and carrying the ΦOXC141 prophage, possess larger pangenomes associated with hypothetical protein genes.

Conclusions:

• Clade I of CC180 serotype 3 Spn emerged as dominant in Portugal post-PCV13, despite antibiotic sensitivity and prophage carriage.
• Additional accessory genome content in Clade I may confer fitness advantages, potentially mitigating costs associated with antibiotic sensitivity.
• Regional variations in Clade I prevalence and pangenome heterogeneity indicate that clade dynamics alone do not fully explain serotype 3 vaccine escape.