OBJECTIVES: Antimicrobial-resistant bacteria are a major global health threat. Mobile genetic elements (MGEs) have been crucial for spreading resistance to new bacterial species, including human pathogens. Understanding how MGEs promote resistance could be essential for prevention. Here we present an investigation of MGEs and their association with resistance genes in pathogenic bacteria collected from 59 diagnostic units during 2020, representing a snapshot of clinical infections from 35 counties worldwide. METHODS: We analysed 3,095 whole-genome sequenced clinical bacterial isolates from over 100 species to study the relationship between resistance genes and MGEs. The mobiliome of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae were further examined for geographic differences, as these species were prevalent in all countries. Genes potentially mobilized by MGEs were identified by finding DNA segments containing MGEs and ARGs preserved in multiple species. Network analysis was used to investigate potential MGE interactions, host range, and transmission pathways. RESULTS: The prevalence and diversity of MGEs and resistance genes varied among species, with E. coli and S. aureus carrying more diverse elements. MGE composition differed between bacterial lineages, indicating strong vertical inheritance. 102 MGEs associated with resistance were found in multiple species, and four of these elements seemed to be highly transmissible as they were found in different phyla. We identified 21 genomic regions containing resistance genes potentially mobilized by MGEs, highlighting their importance in transmitting genes to clinically significant bacteria. CONCLUSION: Resistance genes are spread through various MGEs, including plasmids and transposons. Our findings suggest that multiple factors influence MGE prevalence and their transposability, thereby shaping the MGE population and transmission pathways. Some MGEs have a wider host range, which could make them more important for mobilizing genes. We also identified 103 resistance genes potentially mobilised by MGEs, which could increase their transmissibility to unrelated bacteria.

Alberta Precision Laboratories Alberta Canada

Bacteriology laboratory Centre hospitalier de Valenciennes Valenciennes France

Basic Medical Sciences Department Arab American University Jenin Palestine

Bioanalytica AG Luzern Switzerland

Centro de Investigação em Saéude de Manhiça Manhiça Mozambique

Centro de Investigación para la Salud en América Latina Pontificia Universidad Católica del Ecuador Quinto Pichincha Ecuador

Charalampous Microbiology Department National Reference Laboratory for Antimicrobial Resistance Surveillance Nicosia General Hospital Strovolos Nicosia Cyprus

Chinese University of Hong Kong Shatin Hong Kong

Clinical Laboratory of Microbiology and Virology University Hospital Lozenetz Sofia Bulgaria

Clinical Research Unit of Nanoro National Institutes of Medical Research Ouagadougou Burkina Faso

College of Medicine University of Ibadan Ibadan Oyo State Nigeria

Departamento de Bacteriologia Laboratorio Central de Salud Publico Asunción Paraguay

Department of Clinical and Molecular Microbiology University Hospital Centre Zagreb Zagreb Croatia

Department of Clinical Tropical Medicine Faculty of Tropical Medicine Mahidol University Bangkok Thailand

Department of Industrial Biotechnology Atta ur Rahman School of Applied Biosciences National University of Sciences and Technology Islamabad Pakistan

Department of Laboratory Nouna Health Research Centre Nouna Burkina Faso

Department of Medical Microbiology Motol University Hospital Prague Czech Republic

Department of Medical Sciences National Institute of Health Sariburi Thailand

Department of Medicine and Surgery University of Milano Bicocca Milan Italy

Department of Microbiology and Infection Control Akershus University Hospital Lørenskog Norway

Department of Microbiology PathWest Laboratory Medicine Fiona Stanley Hospital Murdoch Western Australia Australia

Department of Microbiology University Hospital in Plzen Plzen Czech Republic

Department of Microbiology University of Dhaka Dhaka Bangladesh

Department of Pathology and Experimental Therapy Universitat de Barcelona Barcelona Spain

Division of Clinical Bacteriology and Mycology University Hospital Basel Basel Switzerland

Division of Clinical Microbiology Qatif Central Hospital Al Qatif Eastern Province Saudi Arabia

Dronning Ingrids Hospital Nuuk Greenland

Faculty of Pharmacy University of Ibadan Ibadan Oyo State Nigeria

Institute of Microbiology Centre Hospitalier Universitaire de Lille Lille France

Klinisk Mikrobiologisk Afdeling Hvidovre Hospital Hvidovre Denmark

Laboratoire de Microbiologie Clinique Centre Hospitalo universitaire Algiers Algeria

Laboratory Medicine Department Hospital of Lithuanian University of Health Sciences Kaunas Lithuania

Levy Mwanawasa Teaching Hospital Lusaka Zambia

Lusaka Apex Medical School Lusaka Zambia

Medical Microbiology and Immunology University of Pecs Medical School Pecs Hungary

Medical Microbiology Department Karadeniz Technical University Farabi Hospital Trabzon Ortahisar Turkey

Microbiology Department Canberra Hospital Garran Australian Capital Territory Australia

Microbiology Department Hospital de Bellvitge Barcelona Spain

Microbiology Department University Hospital Shefqet Ndroqi Tirana Albania

Microbiology Group Instituto Nacional de Salud Bogotá Colombia

Molecular Diagnostic Section Khyber Teaching Hospital Peshawar Pakistan

National Food Institute Technical University of Denmark Kgs Lyngby Denmark

National Hospital Abuja Abuja Nigeria

National Reference Center for Antimicrobial Resistance National Institute of Public Health research Dr Leopoldo Izquieta Pérez Quito Pichicha Ecuador

Obafemi Awolowo University Ile Ife Nigeria

Otto von Guericke University Magdebourg Germany

Research Unit in Applied Microbiology and Pharmacology of Natural Substances Polytechnic School of Abomey Calavi University of Abomey Calavi Abomey Calavi Cotonou Benin

Sekondi Public Health Laboratory Ghana Health Service Effia Nkwanta Regional Hospital Effia Nkwanta Regional Hospital Ghana

Service de Microbiologie Centre Integré Universitaire de Santé et de services sociaux de l'Estrie Centre Hospitalier Universitaire de Sherbrooke Sherbrooke Québec Canada

Southern Community Laboratories University of Otago Otago Dunedin New Zealand

Training and Research Unit in Applied Sciences and Technologies Biochemistry microbiology University of Dedougou Dedougou Boucle du Mouhon Burkina Faso

University College of Ibadan Ibadan Oyo State Nigeria

University of Joseph KI ZERBO Ouagadouogou Burkina Faso

University Teaching Hospital Lusaka Zambia

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