September 16, 2025Open Access

Streptococcus pneumoniae accessory capsular genes modulate fitness, pathogenicity and immune evasion

JCJia Mun ChanUniversity College London HFHelen R. FlynnThe Francis Crick Institute SKSuyeon KimIncheon St. Mary's Hospital

Key Points

Loss of accessory capsular genes in GPSC10-ST700 increases opsonophagocytic resistance, emphasizing immune evasion.
The study shows that these accessory genes, previously deemed nonfunctional, significantly modulate fitness and the phosphoproteome.
Findings indicate that vaccine escape in serotype 3 strains may occur through capsular locus variations rather than capsule switching.
The research underscores the importance of understanding pneumococcal genetics in tackling infections among vulnerable populations.

Abstract

Globally, Streptococcus pneumoniae disproportionally affects children in resource-poor settings, older adults and people living with HIV. Frequently found as an asymptomatic colonizer of the nasopharynx, this versatile pathogen is a prominent cause of pneumonia, meningitis, bacteraemia and otitis media. Recently, a serotype 3 capsule variant (GPSC10-ST700) has expanded in Malawi with enhanced vaccine escape potential. Here, using a mutational and complementation approach, we show that loss of accessory capsular genes in GPSC10-ST700 contribute to increased opsonophagocytic resistance in this lineage. Although originally thought to be nonfunctional pseudogenes, we show that these genes modulate fitness and the global phosphoproteome in serotype 3 strains. These findings highlight that vaccine escape may be mediated through variations in the pneumococcal capsular locus that enhance fitness, pathogenicity and immune evasion, without capsule switching.

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