Experimental Evolution In Vivo To Identify Selective Pressures during Pneumococcal Colonization.

Area of Science:

• Microbiology
• Evolutionary Biology
• Genomics

Background:

• Experimental evolution is crucial for understanding adaptation to environmental pressures.
• Whole-population genomic sequencing enables tracking of adaptive genotypes.
• In vivo experimental evolution is less common but offers unique insights into pathogenesis.

Purpose of the Study:

• To investigate the population genetic dynamics of Streptococcus pneumoniae during experimental evolution in a murine nasal colonization model.
• To identify gene products under strong selection during repeated colonization cycles.
• To explore the trade-offs associated with adaptation in different host niches.

Main Methods:

• Replicate populations of Streptococcus pneumoniae were propagated through repeated murine nasal colonization.
• Whole-population genomic sequencing was employed to identify selected mutations.
• Targeted gene deletions (dltB) were created to assess fitness consequences.
• Murine models were used to evaluate fitness in nasal colonization and pulmonary infection.

Main Results:

• Frameshift mutations in the dltB gene, affecting d-alanine incorporation into teichoic acids, repeatedly evolved and swept to high frequency.
• dltB deletion conferred a fitness advantage in nasal colonization but a disadvantage in lung infection.
• The fitness trade-off was linked to enhanced adherence to respiratory cells and increased susceptibility to antimicrobial peptides.
• Mutations affecting trace metal transport, metabolism, and biofilm regulation were also selected.

Conclusions:

• In vivo experimental evolution in murine models is effective for studying bacterial adaptation and pathogenesis.
• Repeated nasal colonization selects for mutations impacting bacterial surface charge, conferring niche-specific advantages.
• Adaptations for colonization can lead to trade-offs, impacting fitness in other host environments like the lungs.
• This approach provides insights into pathogen tissue tropisms and evolutionary strategies.