Comparative Genomic Reveals Clonal Heterogeneity in Persistent Staphylococcus aureus Infection.

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Persistent Staphylococcus aureus infections present significant clinical challenges.
• Mechanisms driving S. aureus infection persistence, treatment outcomes, and clinical success require further elucidation.

Purpose of the Study:

• To investigate the genetic relatedness, virulome, and resistome of S. aureus isolates from persistent infections.
• To understand the clonal heterogeneity and adaptational mechanisms contributing to infection persistence.

Main Methods:

• Whole-genome sequencing was performed on fifteen S. aureus isolates from persistent infections.
• Comparative genomic analysis was used to assess genetic relatedness, virulence factors, and antimicrobial resistance genes.

Main Results:

• All isolates originated from a common clone but exhibited heterogeneous virulence factors and antimicrobial resistance profiles.
• Mutations in the rpoB gene correlated with rifampicin resistance and varied oxacillin minimal inhibitory concentrations.
• Acquisition of staphylokinase (sak) and staphylococcal complement inhibitor (scn) genes, linked to immune evasion clusters on temperate phages, was observed in a subset of isolates, leading to hemolysin b (hlb) gene truncation and altered biofilm formation.

Conclusions:

• Comparative genomics revealed significant clonal heterogeneity within persistent S. aureus infections.
• Virulence factors, particularly those associated with temperate phages and immune evasion, may play a crucial role in pathogen persistence and infection course.