Changes in the Genotypic Characteristics of Community-Acquired Methicillin-Resistant Staphylococcus aureus Collected in 244 Medical Facilities in Japan between 2010 and 2018: a Nationwide Surveillance

Although community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide, no nationwide CA-MRSA surveillance has been conducted in Japan to determine the changes in its molecular characteristics over time. We aimed to characterize the molecular epidemiology of Panton-Valentine leucocidin (PVL)-positive CA-MRSA strains collected from across Japan in the past decade. We isolated 1,770 MRSA strains from the skin and pus samples of outpatients of 244 medical facilities in 31 prefectures between 2010 and 2018 (2010, 2012, 2014, 2016, and 2018). Regions, hospitals, and periods in which strains were isolated and patient age group and sex were tabulated. Staphylococcal cassette chromosome mec (SCCmec) typing, detection of virulence factor genes, and antimicrobial susceptibility testing were performed. Whole-genome analysis was performed for the PVL-positive strains isolated in 2018. All strains harbored the mecA gene. Compared to that in 2010, the percentage of SCCmec type IV increased in 2018, with a corresponding increase in the proportion of PVL-positive strains (10% to 26%). Of the isolates obtained in 2018, clonal complex 8 (CC8) was dominant among PVL-positive strains. Core-genome single-nucleotide polymorphism analysis, using whole-genome sequencing, suggested that the CC8 PVL-positive strains spread throughout Japan over the last decade. Furthermore, a unique ST22 clone carrying both the PVL- and toxic shock syndrome toxin-1-encoding genes has emerged. We demonstrated that the molecular epidemiology of CA-MRSA in Japan differs from that in Europe and the United States; thus, it is crucial to monitor the trend of changes in CA-MRSA characteristics in Japan. IMPORTANCE Community-associated MRSA, which is a multidrug-resistant organism and can cause infections in otherwise-healthy individuals, has become a global problem. This paper describes a nationwide surveillance conducted in Japan to investigate changes in molecular epidemiological characteristics of CA-MRSA over the past decade and provides a detailed review of the characteristics of Panton-Valentine leucocidin (PVL)-positive strains isolated in 2018. Although CA-MRSA is rare in Japan to date, we found that the isolation of PVL-positive strains has been increasing over the past decade. In particular, the PVL-positive strains wherein CC8 was dominant exhibited high interstrain similarity, suggesting that a limited number of clones have spread over the past decade. Furthermore, a unique ST22 clone carrying both PVL-encoding and toxic shock syndrome toxin-1-encoding genes has emerged. This study shows that various changes can be observed when molecular epidemiological analysis, combined with next-generation sequencing, is conducted over a long period.