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Title: Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.
Austin Authors: Lee, Jean Y H;Monk, Ian R;Gonçalves da Silva, Anders;Seemann, Torsten;Chua, Kyra Y L ;Kearns, Angela;Hill, Robert;Woodford, Neil;Bartels, Mette D;Strommenger, Birgit;Laurent, Frederic;Dodémont, Magali;Deplano, Ariane;Patel, Robin;Larsen, Anders R;Korman, Tony M;Stinear, Timothy P;Howden, Benjamin P 
Affiliation: Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
National Reference Centre for Staphylococci, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, and Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, USA
Reference Laboratory for Antimicrobial Resistance and Staphylococci, Statens Serum Institut, Copenhagen, Denmark
Monash Infectious Diseases, Centre for Inflammatory Diseases, Monash University, Melbourne, Australia
Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia
Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia
Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Australia
Melbourne Bioinformatics, The University of Melbourne, Melbourne, Australia
Department of Microbiology, Austin Health, Heidelberg, Victoria, Australia
AMRHAI Reference Unit, National Infection Service, Public Health England, London, UK
Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark
National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode Branch, Wernigerode, Germany
Department of Bacteriology, Institute for Infectious Agents, French National Reference Centre for Staphylococci, International Centre for Infectiology Research, Institute for Pharmaceutical and Biological Sciences Of Lyon, University of Lyon, Lyon, France
Issue Date: 2018 2018-09-03
Publication information: Nature microbiology 2018; 3(10): 1175-1185
Abstract: Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.
DOI: 10.1038/s41564-018-0230-7
ORCID: 0000-0001-6046-610X
PubMed URL: 30177740
Type: Journal Article
Appears in Collections:Journal articles

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