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Staphylococcus aureus  sequence type (ST) 72, the predominant community-associated methicillin-resistant  Staphylococcus aureus  (CA-MRSA) lineage in South Korea, has emerged as a major cause of bloodstream infection in hospital settings. However, relatively little information is available regarding the genomic characteristics and dissemination of ST72. Here, we characterized the whole-genome sequence of 24 ST72 isolates from China, along with 83 ST72 genomes from global sources. Of these 107 ST72 isolates, 63 were MRSA and 44 were methicillin-susceptible  S. aureus  (MSSA). Phylogenetic analysis revealed four distinct clades (A, B, C, and D), of which clade D contained only MSSA isolates. By characterizing the evolutionary dynamics of the ST72 lineage, we found that the MRSA from China might not have developed from the MSSA in China. Furthermore, we observed both international transmission of ST72 isolates and interregional transmission within China. The distributions of the SCC mec  and  spa  types of isolates differed among clades. Additionally,  in silico  analyses revealed that the distributions of resistance genes, virulence genes, and mobile genetic elements (MGEs) also differed among isolates of the four clades. This was especially true for clade D isolates, which had the lowest level of antimicrobial resistance and had obtained specific virulence genes such as  tsst-1  by acquisition of specific MGEs. Notably, ST72 MRSA isolates were more antibiotic resistant than ST72 MSSA isolates, but comparably virulent. Our findings provide insight into the potential transmission and genotypic features of ST72 clones across the globe.   IMPORTANCE  Understanding the evolution and dissemination of community-genotype ST72  Staphylococcus aureus  isolates is important, as isolates of this lineage have rapidly spread into hospital settings and caused serious health issues. In this study, we first carried out genome-wide analysis of 107 global ST72 isolates to characterize the evolution and genetic diversity of the ST72 lineage. We found that the MSSA lineage in China might have evolved independently from the MRSA isolates from China, and that ST72 isolates have the potential to undergo both international transmission and interregional transmission within China. The diversity of isolates correlated with distinct acquisitions of SCC mec  elements, antibiotic resistance genes, virulence genes, and mobile genetic elements. The comprehensive information on the ST72 lineage emerging from this study will enable improved therapeutic approaches and rapid molecular diagnosis.

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Comparative Genomic Analysis Provides Insights into the Evolution and Genetic Diversity of Community-Genotype Sequence Type 72 Staphylococcus aureus Isolates