Concurrent Clonal Expansion of Community-Associated Methicillin-resistant Staphylococcus aureus (MRSA) Clones in a Tertiary Hospital

Abstract

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat due to its ability to cause a range of diseases in humans and its resistance to multiple classes of antimicrobials. Community-associated MRSA (CA-MRSA) strains, originating in the community, are increasingly known to underlie hospital infections. However, the dynamics of CA-MRSA clones in hospital settings are not well-characterized. Methods In this study, we conducted a genomic survey of a systematic cross-sectional collection of MRSA isolated over one and a half years in a major tertiary hospital in Jeddah, southwest Saudi Arabia. We subjected 194 isolates recovered from different body sites of 175 patients over two years to whole-genome sequencing and integrated the genomic data with detailed clinical information from electronic health record (EHR) data. We employed a broad range of genomics and text and data mining approaches to decipher the dynamics of MRSA clones, including resistance and virulence mechanisms, and the clinical manifestation of MRSA infections. Results Our results revealed a diverse clonal population underlying the population diversity in the hospital, with six dominant sequence types (STs) concurrently expanding over the past six decades. The major clones in the population harbored hallmarks of CA-MRSA, belonging to ST5 (n = 33), ST672 (n = 36), ST97 (n = 14), ST6 (n = 15), ST88 (n = 19), and ST8 (n = 27). The PVL locus was found in 60% of the ST8 strains and three strains of ST97 and ST88. Phylodynamic analysis showed that ST97, ST6, and ST672 formed more recently than other clones over the past two decades. ST97 carriage was significantly linked to in-hospital mortality and the diagnosis of sepsis. We characterized multiple cases of cross-resistance and showed diverse symptoms associated with colonization/infection by each ST. We further identified the emergence of antimicrobial resistance determinants within each clone and found evidence of the sharing of plasmids carrying antimicrobial resistance genes across multiple MRSA lineages. Conclusion Altogether, the study presents an in-depth analysis of the complex dynamics of MRSA, reflecting the concurrent emergence of multiple clones in a single hospital and highlighting the multiple introductions of CA-MRSA strains into the hospital.