Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination

ObjectivesStaphylococcus aureus is a leading cause of hospital-acquired infections worldwide. Over recent decades, methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to multiple antimicrobials, has emerged as a significant pathogenic strain in both hospital and community settings...

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Main Authors: Ahmed Yousef Alhejaili, Ge Zhou, Heba Halawa, Jiayi Huang, Omniya Fallatah, Raneem Hirayban, Sara Iftikhar, Abrar AlAsmari, Mathew Milner, Manuel Banzhaf, Albandari A. Alzaidi, Ahmad A. Rajeh, Maram Abdulmohsen Al-Otaiby, Sarah S. Alabbad, Doua Bukhari, Abdullah N. Aljurayyan, Alanoud T. Aljasham, Zeyad A. Alzeyadi, Sulaiman M. Alajel, Rawan Hamdan Alanazi, Majed Alghoribi, Mashal M. Almutairi, Arnab Pain, Abiola Senok, Danesh Moradigaravand, Waleed Al Salem
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1602985/full
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author Ahmed Yousef Alhejaili
Ahmed Yousef Alhejaili
Ge Zhou
Heba Halawa
Jiayi Huang
Omniya Fallatah
Raneem Hirayban
Sara Iftikhar
Abrar AlAsmari
Mathew Milner
Manuel Banzhaf
Albandari A. Alzaidi
Ahmad A. Rajeh
Maram Abdulmohsen Al-Otaiby
Sarah S. Alabbad
Doua Bukhari
Abdullah N. Aljurayyan
Alanoud T. Aljasham
Zeyad A. Alzeyadi
Sulaiman M. Alajel
Rawan Hamdan Alanazi
Majed Alghoribi
Mashal M. Almutairi
Arnab Pain
Arnab Pain
Abiola Senok
Abiola Senok
Danesh Moradigaravand
Waleed Al Salem
author_facet Ahmed Yousef Alhejaili
Ahmed Yousef Alhejaili
Ge Zhou
Heba Halawa
Jiayi Huang
Omniya Fallatah
Raneem Hirayban
Sara Iftikhar
Abrar AlAsmari
Mathew Milner
Manuel Banzhaf
Albandari A. Alzaidi
Ahmad A. Rajeh
Maram Abdulmohsen Al-Otaiby
Sarah S. Alabbad
Doua Bukhari
Abdullah N. Aljurayyan
Alanoud T. Aljasham
Zeyad A. Alzeyadi
Sulaiman M. Alajel
Rawan Hamdan Alanazi
Majed Alghoribi
Mashal M. Almutairi
Arnab Pain
Arnab Pain
Abiola Senok
Abiola Senok
Danesh Moradigaravand
Waleed Al Salem
author_sort Ahmed Yousef Alhejaili
collection DOAJ
description ObjectivesStaphylococcus aureus is a leading cause of hospital-acquired infections worldwide. Over recent decades, methicillin-resistant Staphylococcus 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 systematic Staphylococcus aureus collection obtained from 34 hospitals across all provinces of KSA, from diverse body sites between 2022 and 2024. The dataset comprised 581 MRSA and 31 methicillin-susceptible Staphylococcus 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 retrieve the complete plasmid content.ResultsThe population displayed remarkable diversity, comprising 48 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 by cfr-carrying plasmids and mutations in the vraR gene (involved in cell-wall stress response) and the murF gene (involved in 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 of blaZ-containing plasmids and the sharing of erm(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.
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spelling doaj-art-5aac8ce36245434db8e0aa4f9fa5e4da2025-08-20T02:31:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.16029851602985Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance disseminationAhmed Yousef Alhejaili0Ahmed Yousef Alhejaili1Ge Zhou2Heba Halawa3Jiayi Huang4Omniya Fallatah5Raneem Hirayban6Sara Iftikhar7Abrar AlAsmari8Mathew Milner9Manuel Banzhaf10Albandari A. Alzaidi11Ahmad A. Rajeh12Maram Abdulmohsen Al-Otaiby13Sarah S. Alabbad14Doua Bukhari15Abdullah N. Aljurayyan16Alanoud T. Aljasham17Zeyad A. Alzeyadi18Sulaiman M. Alajel19Rawan Hamdan Alanazi20Majed Alghoribi21Mashal M. Almutairi22Arnab Pain23Arnab Pain24Abiola Senok25Abiola Senok26Danesh Moradigaravand27Waleed Al Salem28Ministry of Health, Riyadh, Saudi ArabiaNewcastle University Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United KingdomLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaFaculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, United KingdomMinistry of Health, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi ArabiaExecutive Department of Reference Laboratories, Research and Laboratories Sector, Saudi Food and Drug Authority, Riyadh, Saudi ArabiaMinistry of Environment Water and Agriculture, Riyadh, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia0Pathogen Genomics Laboratory, KAUST Center of Excellence for Smart Health and Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia1International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan2College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates3School of Dentistry, Cardiff University, Cardiff, United KingdomLaboratory of Infectious Disease Epidemiology, KAUST Center of Excellence for Smart Health and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaMinistry of Health, Riyadh, Saudi ArabiaObjectivesStaphylococcus aureus is a leading cause of hospital-acquired infections worldwide. Over recent decades, methicillin-resistant Staphylococcus 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 systematic Staphylococcus aureus collection obtained from 34 hospitals across all provinces of KSA, from diverse body sites between 2022 and 2024. The dataset comprised 581 MRSA and 31 methicillin-susceptible Staphylococcus 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 retrieve the complete plasmid content.ResultsThe population displayed remarkable diversity, comprising 48 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 by cfr-carrying plasmids and mutations in the vraR gene (involved in cell-wall stress response) and the murF gene (involved in 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 of blaZ-containing plasmids and the sharing of erm(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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1602985/fullMRSAMSSAbloodstream infectionSTprecision epidemiologyKingdom of Saudi Arabia
spellingShingle Ahmed Yousef Alhejaili
Ahmed Yousef Alhejaili
Ge Zhou
Heba Halawa
Jiayi Huang
Omniya Fallatah
Raneem Hirayban
Sara Iftikhar
Abrar AlAsmari
Mathew Milner
Manuel Banzhaf
Albandari A. Alzaidi
Ahmad A. Rajeh
Maram Abdulmohsen Al-Otaiby
Sarah S. Alabbad
Doua Bukhari
Abdullah N. Aljurayyan
Alanoud T. Aljasham
Zeyad A. Alzeyadi
Sulaiman M. Alajel
Rawan Hamdan Alanazi
Majed Alghoribi
Mashal M. Almutairi
Arnab Pain
Arnab Pain
Abiola Senok
Abiola Senok
Danesh Moradigaravand
Waleed Al Salem
Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
Frontiers in Microbiology
MRSA
MSSA
bloodstream infection
ST
precision epidemiology
Kingdom of Saudi Arabia
title Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
title_full Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
title_fullStr Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
title_full_unstemmed Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
title_short Methicillin-resistant Staphylococcus aureus in Saudi Arabia: genomic evidence of recent clonal expansion and plasmid-driven resistance dissemination
title_sort methicillin resistant staphylococcus aureus in saudi arabia genomic evidence of recent clonal expansion and plasmid driven resistance dissemination
topic MRSA
MSSA
bloodstream infection
ST
precision epidemiology
Kingdom of Saudi Arabia
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1602985/full
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