Global insights into the genome dynamics of associated with antimicrobial resistance, virulence, and genomic adaptations among clonal lineages.

Background: is a significant cause of healthcare-associated infections, with rising antimicrobial resistance complicating treatment. This study offers a genomic analysis of , focusing on sequence types (STs), global distribution, antibiotic resistance genes, and virulence factors in its chromosomal and plasmid DNA.

Methods: A total of 19,711 genomes were retrieved from GenBank. Prokka was used for genome annotation, and multi-locus sequence typing (MLST) identified STs. Pan-genome analysis with Roary identified core and accessory genes. Antibiotic resistance genes, virulence factors, and toxins were detected using the CARD and VFDB databases, and the ABRicate software. Statistical analyses and visualizations were performed in R.

Results: Among 366 identified STs, ST1 (1,326 isolates), ST2 (1,141), ST11 (893), and ST42 (763) were predominant. Trends of genome streamlining included reductions in chromosomal length, gene count, protein-coding genes, and pseudogenes. Common antibiotic resistance genes- (99.46%), (99.63%), and (99.67%)-were nearly ubiquitous. Rare resistance genes like , , and appeared in only 0.005% of genomes. Vancomycin susceptibility-reducing cluster genes were detected at low frequencies. Virulence factors showed variability, with highly prevalent genes such as (99.62%), (99.60%), and (99.60%). Moderately distributed genes included (54.61%) and (79.02%). Toxin genes (91.26%), (89.67%), and (89.06%) were widespread, while binary toxin genes (26.19%) and (26.26%) were less common. Toxin gene prevalence, particularly and , showed a gradual decline over time, with sharper reductions for and . Gene presence patterns (GPP-1) for resistance, virulence, and toxin genes were primarily linked to ST2, ST42, and ST8.

Conclusion: This study highlights 's adaptability and genetic diversity. The decline in toxin genes reflects fewer toxigenic isolates, but the bacterium's increasing preserved resistance factors and virulence genes enable its rapid evolution. ST2, ST42, and ST8 dominate globally, emphasizing the need for ongoing monitoring.