Antimicrobial resistance (AMR) threatens global health, and among the organisms of greatest concern is methicillin-resistant Staphylococcus aureus (MRSA). As part of a national effort to understand the evolution and prevalence of this bacterium, researchers conducted a comprehensive genomic surveillance study in Japan, focusing on Staphylococcus aureus strains isolated from bloodstream infections between 2019 and 2020.
This ambitious study involved the genome sequencing and antimicrobial susceptibility testing of 580 S. aureus isolates. Researchers investigated three predominant strains—designated clonal complexes (CC) 1, 5, and 8—aiming to map their clinical significance and regional distribution across eastern and western Japan. They compared the genomic data with historical samples collected from 1994 to 2000 to shed light on the evolutionary patterns and emerging high-risk clones.
The findings revealed alarming statistics: the ST764-SCCmecII strain was linked to a staggering 48% mortality rate within 30 days of hospitalization. This particular clone is a descendant of the New York/Japan clone (ST5-SCCmecII) and has undergone significant evolutionary changes, acquiring antimicrobial resistance and virulence factors through the exchange of genetic material.
MRSA is a particularly dangerous pathogen, responsible for severe systemic infections. In Japan, bloodstream infections caused by S. aureus have been steadily increasing, resulting in thousands of fatalities each year. For instance, studies previously indicated that in 2017, there were an estimated 17,157 deaths attributed to S. aureus infections in Japan, of which a significant proportion were due to MRSA.
In the current genomic surveillance study, the researchers focused on identifying the distribution and characteristics of the strains. Their analyses used Bayesian hierarchical clustering, which revealed 13 distinct genetic clusters among the isolates collected from patients. Notably, clonal complex 8 (CC8), mainly represented by the ST8 strain, emerged as a predominant lineage causing infections in both eastern and western Japan, although the proportions differed across regions.
Of those isolates, a notable 46.4% were methicillin-resistant Staphylococcus aureus (MRSA), with the majority belonging to the SCCmecIV group. In eastern Japan, the ST1 strain was particularly predominant, while in western Japan, ST8 showcased higher prevalence rates.
One of the most significant discoveries made by the researchers involves the assessment of mortality rates associated with different clonal strains. The ST764-SCCmecII strain not only exhibited the highest mortality rate among those studied but also indicated a concerning trend in hospital settings. As the authors observed, the ST764 had diverged from the New York/Japan clone, showcasing the staggering potential of MRSA to adapt and evolve. “This is a new era of MRSA demographics in Japan,” wrote the authors.
The study encapsulates a frustrating reality: despite efforts to monitor and control the prevalence of such pathogens, MRSA continues to present new challenges to public health officials. The emergence of the ST764 strain bloomed from a backdrop of extensive genetic exchange occurring within bacterial populations, enabled by the presence of mobile genetic elements that facilitate resistance traits.
In comparing the 2019–2020 isolates against those from 1994–2000, the researchers identified shifts in clonal distribution and antimicrobial resistance. This historical perspective allowed them to deduce that improvements in clinical practices had contributed to a decline in overall MRSA prevalence in some cohorts. For example, death rates attributed to MRSA in Japan decreased from 34% to 24.6% between 2011 and 2017. Nonetheless, the rising emergence of the ST764 remains troubling, indicating a potential resurgence in virulent strains.
The authors call for improved genomic surveillance and understanding of the genetic mechanisms driving the evolution of such high-risk clones. “Our study provides a blueprint for national genomic surveillance that integrates clinical data and enables the identification and evolutionary characterization of a high-risk clone,” concluded the authors, emphasizing the necessity for ongoing monitoring and research in tackling antimicrobial resistance.
The findings of this study highlight critical insights into the landscape of MRSA in Japan, underscoring the urgency of addressing antimicrobial resistance to ensure patient safety and effective treatment strategies.
