Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes

Area of Science:

• Microbiology
• Infectious Diseases
• Genomics

Background:

• Streptococcus pneumoniae is a common nasopharyngeal colonizer causing serious infections.
• Recurrent infections in immunocompromised individuals pose significant clinical challenges.
• Understanding pathogen evolution during chronic colonization is crucial for effective treatment.

Purpose of the Study:

• To investigate the genomic and phenotypic evolution of Streptococcus pneumoniae during recurrent pneumonia in a pediatric patient.
• To identify genetic mechanisms underlying serotype switching and antimicrobial resistance.
• To evaluate the effectiveness of different pneumococcal vaccines in eliciting protective immunity.

Main Methods:

• Collection and whole-genome sequencing of 10 S. pneumoniae isolates from sputum over 25 months.
• Analysis of single nucleotide polymorphisms (SNPs) to assess genomic relatedness and identify mutations.
• Serotyping of isolates to determine capsule types.
• Assessment of immune response to pneumococcal vaccination through opsonic activity assays.

Main Results:

• Ten S. pneumoniae isolates were clonally related, indicating a single strain's persistence and evolution.
• Serotype switching from 6B to 6A was observed, linked to a mutation in the wciP gene.
• Mutations in parC and gyrA genes conferred fluoroquinolone resistance.
• Pre-existing vaccinations (7-valent and 23-valent) showed limited efficacy, while the 13-valent vaccine significantly boosted opsonic activity against serotypes 6A and 6B.

Conclusions:

• A single, evolving S. pneumoniae strain caused recurrent pneumonia, exhibiting serotype switching and antimicrobial resistance.
• Phenotypic variations occurred during asymptomatic colonization or horizontal transmission.
• The 13-valent pneumococcal conjugate vaccine enhanced protective immunity, potentially preventing future relapses.