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    Nature. 2022 Jan 5. doi: 10.1038/s41586-021-04265-w. pii: 10.1038/s41586-021-04265-w
    Emergence of methicillin resistance predates the clinical use of antibiotics.
    Larsen J1,  Raisen CL2,  Ba X3,  Sadgrove NJ4,  Padilla-González GF5,  Simmonds MSJ6,  Loncaric I7,  Kerschner H8,  Apfalter P9,  Hartl R10,  Deplano A11,  Vandendriessche S12,  Černá Bolfíková B13,  Hulva P14,  Arendrup MC15,  Hare RK16,  Barnadas C17,  Stegger M18,  Sieber RN19,  Skov RL20,  Petersen A21,  Angen Ø22,  Rasmussen SL23,  Espinosa-Gongora C24,  Aarestrup FM25,  Lindholm LJ26,  Nykäsenoja SM27,  Laurent F28,  Becker K29,  Walther B30,  Kehrenberg C31,  Cuny C32,  Layer F33,  Werner G34,  Witte W35,  Stamm I36,  Moroni P37,  Jørgensen HJ38,  de Lencastre H39,  Cercenado E40,  García-Garrote F41,  Börjesson S42,  Hæggman S43,  Perreten V44,  Teale CJ45,  Waller AS46,  Pichon B47,  Curran MD48,  Ellington MJ49,  Welch JJ50,  Peacock SJ51,  Seilly DJ52,  Morgan FJE53,  Parkhill J54,  Hadjirin NF55,  Lindsay JA56,  Holden MTG57,  Edwards GF58,  Foster G59,  Paterson GK60,  Didelot X61,  Holmes MA62,  Harrison EM63,  Larsen AR64
    Author information
    1Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark. jrl@ssi.dk.
    2Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    3Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    4Royal Botanic Gardens, Kew, Richmond, UK.
    5Royal Botanic Gardens, Kew, Richmond, UK.
    6Royal Botanic Gardens, Kew, Richmond, UK.
    7Institute of Microbiology, University of Veterinary Medicine, Vienna, Austria.
    8National Reference Center for Antimicrobial Resistance and Nosocomial Infections, Institute for Hygiene, Microbiology and Tropical Medicine, Ordensklinikum Linz Elisabethinen, Linz, Austria.
    9National Reference Center for Antimicrobial Resistance and Nosocomial Infections, Institute for Hygiene, Microbiology and Tropical Medicine, Ordensklinikum Linz Elisabethinen, Linz, Austria.
    10National Reference Center for Antimicrobial Resistance and Nosocomial Infections, Institute for Hygiene, Microbiology and Tropical Medicine, Ordensklinikum Linz Elisabethinen, Linz, Austria.
    11National Reference Centre-Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université libre de Bruxelles, Brussels, Belgium.
    12National Reference Centre-Staphylococcus aureus, Department of Microbiology, Hôpital Erasme, Université libre de Bruxelles, Brussels, Belgium.
    13Department of Animal Science and Food Processing, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Prague, Czech Republic.
    14Department of Zoology, Charles University, Prague, Czech Republic.
    15Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    16Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    17Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    18Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    19Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    20Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark.
    21Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    22Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    23Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    24Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
    25National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
    26Expert Microbiology Unit, Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.
    27Microbiology Unit, Finnish Food Authority, Helsinki, Finland.
    28Bacteriology Department and French National Reference Center for Staphylococci, Hospices Civils de Lyon, University of Lyon, Lyon, France.
    29Friedrich Loeffler-Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
    30Institute of Microbiology and Epizootics, Veterinary Faculty, Freie Universität Berlin, Berlin, Germany.
    31Institute for Veterinary Food Science, Justus-Liebig University Giessen, Giessen, Germany.
    32National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode, Germany.
    33National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode, Germany.
    34National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode, Germany.
    35National Reference Centre for Staphylococci and Enterococci, Division Nosocomial Pathogens and Antibiotic Resistances, Department of Infectious Diseases, Robert Koch Institute, Wernigerode, Germany.
    36Vet Med Labor GmbH, Kornwestheim, Germany.
    37Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Lodi, Italy.
    38Norwegian Veterinary Institute, Ås, Norway.
    39Laboratory of Molecular Genetics, ITQB NOVA, Oeiras, Portugal.
    40Servicio de Microbiología, Hospital Universitario Lucus Augusti, Lugo, Spain.
    41Servicio de Microbiología, Hospital Universitario Lucus Augusti, Lugo, Spain.
    42Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    43Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    44Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland.
    45Department of Bacteriology, Animal and Plant Health Agency, Weybridge, UK.
    46Animal Health Trust, Newmarket, UK.
    47Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, UK Health Security Agency, London, UK.
    48Clinical Microbiology and Public Health Laboratory, UK Health Security Agency, Addenbrooke's Hospital, Cambridge, UK.
    49Clinical Microbiology and Public Health Laboratory, UK Health Security Agency, Addenbrooke's Hospital, Cambridge, UK.
    50Department of Genetics, University of Cambridge, Cambridge, UK.
    51Department of Medicine, University of Cambridge, Cambridge, UK.
    52Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    53Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    54Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    55Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    56Institute of Infection and Immunity, St George's, University of London, London, UK.
    57School of Medicine, University of St Andrews, St Andrews, UK.
    58Scottish MRSA Reference Laboratory, NHS Greater Glasgow and Clyde, Stobhill Hospital, Glasgow, UK.
    59SRUC Veterinary Services, Inverness, UK.
    60The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, UK.
    61School of Life Sciences and Department of Statistics, University of Warwick, Warwick, UK.
    62Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    63Department of Medicine, University of Cambridge, Cambridge, UK.
    64Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Abstract

    The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.


    © 2022. The Author(s).

    Publikations ID: 34987223
    Quelle: öffnen
     
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