Within-host genomic evolution of methicillin-resistant Staphylococcus aureus in long-term carriers

Area of Science:

• Microbiology
• Genomics
• Evolutionary Biology

Background:

• Understanding the genomic evolution of Staphylococcus aureus, particularly methicillin-resistant Staphylococcus aureus (MRSA), is crucial for comprehending bacterial adaptation.
• Long-term carriage of MRSA presents unique opportunities to study within-host evolution.

Purpose of the Study:

• To determine the mutation rate in MRSA during long-term carriage.
• To investigate if factors like household transmission or continued exposure influence the mutation rate.

Main Methods:

• Whole-genome sequencing (WGS) was performed on 424 MRSA isolates from 121 long-term carriers (carriage time 4-11 years).
• Core genome multilocus sequence typing (cgMLST) and single-nucleotide polymorphism (SNP) analyses were used for pairwise comparisons.
• Mutation rates were calculated, excluding presumed recombination, and stratified by exposure subgroups.

Main Results:

• A median within-host mutation rate of 4.9 SNPs/genome/year was observed in long-term MRSA carriers.
• No significant differences in mutation rates were found between household members, individuals with presumed continued exposure (e.g., travelers), and those without known continued exposure.
• Single-nucleotide polymorphisms (SNPs) were found to occur randomly across the genome, with no identified hotspots.

Conclusions:

• The genomic mutation rate in MRSA is relatively stable within long-term carriers, irrespective of their exposure patterns.
• SNPs accumulate randomly, suggesting no specific genomic regions are preferentially targeted for mutation during sustained MRSA carriage.