The DNA Phosphorothioation Restriction-Modification System Influences the Antimicrobial Resistance of Pathogenic...

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Bacterial defense systems like restriction-modification (R-M) and CRISPR-Cas are crucial for antimicrobial resistance (AMR).
• A novel DNA phosphorothioate (PT) modification-based R-M system is prevalent in Bacteria and Archaea, but its role in AMR is unknown.

Purpose of the Study:

• To investigate the role of PT R-M systems in bacterial AMR.
• To determine if PT R-M systems influence the acquisition of AMR genes via horizontal gene transfer (HGT).

Main Methods:

• Analysis of AMR gene distribution on mobile genetic elements (MGEs) in clinical pathogenic bacteria.
• Pangenome analysis and MGE prediction to assess gene variation and HGT frequency.
• Comparative analysis of AMR gene acquisition in different bacterial species (e.g., Klebsiella pneumoniae, Salmonella enterica, Escherichia coli).

Main Results:

• PT R-M systems significantly reduce the prevalence of HGT-derived AMR genes in bacterial genomes.
• The presence of PT R-M correlates with lower HGT frequency, irrespective of the bacteria's general tendency to acquire AMR genes.
• Strains with PT R-M have fewer AMR genes linked to plasmids, prophages, or integrating MGEs (iMGEs), though inhibition levels vary.

Conclusions:

• The PT R-M system acts as a barrier against the acquisition of HGT-derived AMR genes by suppressing HGT frequency.
• No direct correlation exists between the genetic background of PT R-M-harboring strains and the quantity or types of AMR genes.
• Bacterial species exhibit differential preferences for acquiring MGE-derived AMR genes, with no observed coevolution between PT R-M and core bacterial genes.