Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo

Area of Science:

• Microbiology
• Genetics
• Infectious Diseases

Background:

• Staphylococcus aureus is a significant human and animal pathogen.
• Mobile genetic elements (MGE), like bacteriophages and plasmids, are crucial for S. aureus adaptation, virulence, and host colonization.
• Antimicrobial-resistant S. aureus in livestock pose a zoonotic risk.

Purpose of the Study:

• To investigate the role of MGE transfer in S. aureus adaptation during host colonization.
• To compare in vivo and in vitro genetic dynamics of S. aureus.
• To experimentally demonstrate bacteriophage recombination and integration in vivo.

Main Methods:

• Experimental evolution using gnotobiotic piglets.
• Co-colonization with human- and pig-associated S. aureus variants (clonal complex 398).
• Whole genome sequencing to track genetic changes over 16 days.

Main Results:

• Human S. aureus isolate showed enhanced survival during co-colonization compared to in vitro growth.
• Rapid and extensive horizontal gene transfer of MGE (bacteriophages, plasmids) from pig to human isolates occurred within hours.
• No core genome polymorphisms were observed, emphasizing MGE's role in adaptation.
• Bacteriophage recombination and integration into novel sites were observed experimentally in vivo.
• Bacterial populations diversified within piglets, with each piglet developing unique variants.

Conclusions:

• Horizontal gene transfer of MGE is a highly frequent and significant driver of S. aureus adaptation and diversification in vivo.
• MGE transfer facilitates rapid adaptation of S. aureus to new host environments.
• Experimental evolution in gnotobiotic models provides novel insights into bacterial evolution and gene transfer dynamics.