Pneumococcal genetic variability in age-dependent bacterial carriage.

Area of Science:

• Microbiology and Immunology
• Genetics and Genomics
• Vaccinology

Background:

• Pneumococcal carriage varies significantly between pediatric and adult populations.
• Host immune factors are known contributors to age-specific pneumococcal carriage differences.
• The influence of pathogen genetic variation on age-associated carriage remains less understood.

Purpose of the Study:

• To investigate the role of pathogen genetic factors in age-specific pneumococcal carriage.
• To identify potential targets for improved pneumococcal vaccine formulations.
• To analyze genome-wide associations between host age and pneumococcal genetic variation.

Main Methods:

• Genome sequencing of pneumococcal isolates from a large carriage cohort of children and adults.
• Integration of data from an existing age-stratified carriage study.
• Compilation of a pathogen genetic variation dictionary (serotype, strain, SNPs, COGs) and genome-wide association analysis with host age.

Main Results:

• Age-dependent pneumococcal colonization showed heritability, stronger in the second cohort (h² = 0.56).
• Serotype and genetic background (strain) explained a proportion of this heritability in both cohorts.
• A single candidate association was identified upstream of a serine-rich glycoprotein adhesin gene (p=1.2 × 10⁻⁹).

Conclusions:

• Pathogen genome variation has a small, population-variable effect on pneumococcal carriage between children and adults.
• The observed effects are not driven by strong individual gene impacts.
• Findings support adaptive vaccination strategies targeting dominant serotypes and pathogen population composition.