Abstract
Antimicrobial resistance is a global health concern, and methicillin-resistant Staphylococcus aureus (MRSA) is one of the highest-priority organisms exhibiting this phenotype. Here, we performed a national surveillance integrating patient clinical data of S. aureus isolated from bloodstream infections. We performed genome sequencing, standardized antimicrobial susceptibility testing, and collected clinical metadata of 580 S. aureus isolates collected during 2019-2020. We focused on three predominant clonal complexes (CC1, CC5, and CC8) and assesses their microbiological and clinical significance, as well as their distribution across eastern and western Japan. Furthermore, we conducted a genomic comparison of the isolates of 2019-2000 with those of 1994-2000 and investigated the evolutionary trajectory of emerging clones from the three dominant clonal complexes. We revealed that the emerging MRSA ST764-SCCmecII showed the highest mortality rate within 30 days of hospitalization. This high-risk clone diverged from the New York/Japan clone (ST5-SCCmecII), which was inferred to have undergone repeated infections with phages carrying superantigen toxin genes and acquired antimicrobial resistance genes via mobile genetic elements, leading to its emergence around 1994. Overall, we provide a blueprint for a national genomic surveillance study that integrates clinical data and enables the identification and evolutionary characterization of a high-risk clone.