Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Area of Science:

• Genetics
• Microbiology
• Immunology

Background:

• Streptococcus pneumoniae is a common bacteria causing invasive diseases like meningitis.
• Host and pathogen genetic variations influence disease risk and severity, but the extent is not fully understood.

Purpose of the Study:

• To quantify the contributions of human and pneumococcal genetic variation to invasive pneumococcal disease.
• To identify specific genetic factors in both host and pathogen associated with disease susceptibility, severity, and invasiveness.

Main Methods:

• Genome-wide association study (GWAS) of human populations.
• Analysis of pneumococcal genomes.
• Human-bacteria interaction analysis.

Main Results:

• Human genetic variation explains approximately 50% of susceptibility and 33% of severity variation in pneumococcal meningitis, with CCDC33 variants identified.
• Pneumococcal genetic variation accounts for 70% of invasive potential but does not affect disease severity.
• Serotype alone is insufficient to predict invasiveness; pneumococcal genes pspC and zmpD are implicated in invasive potential.

Conclusions:

• Host genetics plays a substantial role in pneumococcal meningitis susceptibility and severity.
• Pneumococcal genetic factors, beyond serotype, are critical for disease invasiveness.
• Identified pneumococcal genes (pspC, zmpD) are promising targets for novel, broadly-acting pneumococcal vaccines.