Genetic Diversity of Methicillin-Resistant Staphylococcus Aureus Among Japanese Inpatients in the Early 1980s

Abstract Background: Methicillin-resistant Staphylococcus aureus (MRSA) was recognized as a serious nosocomial pathogen in Japan starting in the early 1980s. Limited genotypic characteristics on healthcare-associated MRSA (HA-MRSA) associated with “hospital MRSA panics” in Japan in this era. Therefore, this study aimed to determine the characteristics of Japanese HA-MRSA strains in the early 1980s and their linkage with current MRSA strains.Methods: For 194 S. aureus strains isolated in the early 1980s, we determined methicillin resistance phenotypically and genotypically and performed multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and whole-genome sequencing. Results: Twenty mecA-positive MRSA (10.3%), 8 mecA-negative MRSA (4.1%) and 3 mecA-positive methicillin-susceptible S. aureus (MSSA) (1.5%) strains were identified. The frequent sequence type (ST) was ST30 (n=11), followed by ST5 (n=8), ST81 (n=4), and ST247 (n=3). Rates of SCCmec types I, II, and IV were 65.2%, 13.0%, and 17.4%, respectively. ST30-SCCmec I (n=7) and ST5-SCCmec I (n=5) were predominant genotypes. Only two strains exhibited tst-positive ST5-SCCmec II, which is the current Japanese HA-MRSA genotype. Moreover, 73.3% of SCCmec type I strains were susceptible to imipenem compared with SCCmec type II strains (0%). All ST30 strains shared a common ancestor with strain 55/2053, which resulted in a global pandemic of Panto-Valentine leukocidin (PVL)-positive and penicillin-resistant MSSA spread in Europe and the United States in the 1950s. Conclusions: Our results demonstrated the heterogeneous population structure of Japanese HA-MRSA during the early 1980s, which comprised diverse clones that are mostly rare in recent years. The shift to the current homogenous population structure of HA-MRSA strains consisting of tst-positive ST5-SCCmec II might result from the clinical introduction of new antimicrobials including imipenem.