Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and...

Area of Science:

• Microbiology
• Genetics
• Immunology

Background:

• Patients with sickle cell disease (SCD) are highly susceptible to invasive pneumococcal infections.
• Standard care includes pneumococcal vaccination, antibiotic prophylaxis, and treatment.

Purpose of the Study:

• To investigate the impact of SCD and related interventions on the genetic makeup of pneumococcal bacteria.
• To understand the evolution of pneumococcal strains in individuals with SCD.

Main Methods:

• Genomic sequencing of over 300 pneumococcal isolates from SCD patients over 20 years.
• Utilized a murine SCD model with Tn-seq mutagenesis to identify pneumococcal genes under selective pressure.
• Correlated genetic findings with SCD pathophysiology.

Main Results:

• Pneumococcal strains in SCD patients maintained invasiveness but shifted away from vaccine serotypes.
• Identified specific genetic adaptations in antibiotic resistance, capsule biosynthesis, metabolism, and metal transport.
• Discovered 60 noncapsular pneumococcal genes under selective pressure in SCD, linked to disease pathology.
• Found distinct virulence determinants and loss of protective antigen capacity over time in SCD.

Conclusions:

• Pneumococcal strains in SCD patients exhibit unique evolutionary trajectories.
• Understanding bacterial pathogenesis in high-risk populations like SCD is crucial for effective disease management and vaccine development.