Methicillin-resistantStaphylococcus aureusin Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
Authors: Alhejaili Ahmed Yousef , Zhou Ge , Halawa Heba , Huang Jiayi , Fallatah Omniya , Hirayban Raneem , Iftikhar Sara , AlAsmari Abrar , Milner Mathew , Banzhaf Manuel , Alzaidi Albandari A. , Rajeh Ahmad A. , Al-Otaiby Maram Abdulmohsen , Alabbad Sarah S. , Bukhari Doua , Aljurayyan Abdullah N. , Aljasham Alanoud T. , Alzeyadi Zeyad A. , Alajel Sulaiman M. , Alanazi Rawan Hamdan , Alghoribi Majed , Almutairi Mashal M. , Pain Arnab , Senok Abiola , Moradigaravand Danesh , Salem Waleed Al 
Published: February 2025

AbstractObjectivesStaphylococcus aureusis a leading cause of hospital-acquired infections worldwide. Over recent decades, methicillin-resistantStaphylococcus aureus(MRSA), which is resistant to multiple antimicrobials, has emerged as a significant pathogenic strain in both hospital and community settings. The rapid emergence and dissemination of MRSA clones are driven by a dynamic and evolving population, spreading swiftly across regions on epidemiological time scales. Despite the vast geographical expanse and diverse demographics of the Kingdom of Saudi Arabia and the broader West Asia region, the population diversity of MRSA in hospitals in these areas remains underexplored.MethodsWe conducted a large-scale genomic analysis of a systematicStaphylococcus aureuscollection obtained from 34 hospitals across all provinces of KSA, from diverse infection sites between 2022 and 2024. The dataset comprised 582 MRSA and 30 methicillin-susceptibleStaphylococcus aureus(MSSA) isolates, all subjected to whole-genome sequencing. A combination of phylogenetic and population genomics approaches was utilized to analyze the genomic data. Hybrid sequencing approach was employed to retrive the complete plasmid content.ResultsThe population displayed remarkable diversity, comprising 35 distinct sequence types (STs), with the majority harboring community-associated SCCmec loci (types IVa, V/VII, and VI). Virulence factors associated with community-acquired MRSA (CA-MRSA), including Panton-Valentine Leukocidin (PVL) genes, were identified in 12 distinct STs. Dominant clones, including ST8-t008 (USA300), ST88-t690, ST672-t3841, ST6-t304, and ST5-t311, were associated with infections at various body sites and were widely disseminated across the country. Linezolid and vancomycin resistance were mediated bycfr-carrying plasmids and mutations in thevraRgene (involved in cell-wall stress response) and themurFgene (peptidoglycan biosynthesis) in five isolates, respectively. Phylodynamic analysis revealed rapid expansion of the dominant clones, with their emergence estimated to have occurred 10–20 years ago. Plasmidome analysis uncovered a diverse repertoire ofblaZ-containing plasmids and the sharing oferm(C)-encoding plasmids among major clades. The acquisition of plasmids coincided with clonal expansion.ConclusionsOur results highlight the recent concurrent expansion and geographical dissemination of CA-MRSA clones across hospitals. These findings also underscore the interplay between clonal spread and horizontal gene transfer in shaping the resistance landscape of MRSA.