Streptococcus pneumoniae clonal complex 199: genetic diversity and tissue-specific virulence

Area of Science:

• Microbiology
• Genetics
• Immunology

Background:

• Streptococcus pneumoniae causes otitis media and invasive diseases.
• Pneumococcal conjugate vaccines led to increased disease from serotype 19A clonal complex (CC)199.
• CC199 isolates exhibit genetic diversity and are associated with disease replacement.

Purpose of the Study:

• Describe genetic diversity within CC199 isolates.
• Compare CC199 19A and 15B/C isolates in a chinchilla disease model.
• Identify accessory genes linked to tissue-specific pneumococcal disease.

Main Methods:

• Comparative genome hybridization of CC199 isolates.
• Chinchilla model to assess colonization and disease.
• Correspondence analysis to identify tissue-specific genes.
• Whole-genome sequencing of a hypervirulent isolate.

Main Results:

• CC199 phylogeny divided into carriage and disease clades.
• Disease clade isolates showed faster bacteremia than carriage clade isolates.
• Specific genes (spr0282, SP0163, SP0463, SPN05002, RD8a) associated with carriage or specific disease sites.
• Hypervirulent isolate possessed a novel 20 kb phage-like region.

Conclusions:

• Genetic factors beyond serotype modulate CC199 virulence.
• Findings have implications for long-term pneumococcal conjugate vaccine effectiveness.
• Future vaccines targeting common proteins may reduce carriage and disease.