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dc.contributor.authorLarsen, Jesper
dc.contributor.authorRaisen, Claire L
dc.contributor.authorBa, Xiaoliang
dc.contributor.authorSadgrove, Nicholas J
dc.contributor.authorPadilla-González, Guillermo F
dc.contributor.authorSimmonds, Monique S J
dc.contributor.authorLoncaric, Igor
dc.contributor.authorKerschner, Heidrun
dc.contributor.authorApfalter, Petra
dc.contributor.authorHartl, Rainer
dc.contributor.authorDeplano, Ariane
dc.contributor.authorVandendriessche, Stien
dc.contributor.authorČerná Bolfíková, Barbora
dc.contributor.authorHulva, Pavel
dc.contributor.authorArendrup, Maiken C
dc.contributor.authorHare, Rasmus K
dc.contributor.authorBarnadas, Céline
dc.contributor.authorStegger, Marc
dc.contributor.authorSieber, Raphael N
dc.contributor.authorSkov, Robert L
dc.contributor.authorPetersen, Andreas
dc.contributor.authorAngen, Øystein
dc.contributor.authorRasmussen, Sophie L
dc.contributor.authorEspinosa-Gongora, Carmen
dc.contributor.authorAarestrup, Frank M
dc.contributor.authorLindholm, Laura J
dc.contributor.authorNykäsenoja, Suvi M
dc.contributor.authorLaurent, Frederic
dc.contributor.authorBecker, Karsten
dc.contributor.authorWalther, Birgit
dc.contributor.authorKehrenberg, Corinna
dc.contributor.authorCuny, Christiane
dc.contributor.authorLayer, Franziska
dc.contributor.authorWerner, Guido
dc.contributor.authorWitte, Wolfgang
dc.contributor.authorStamm, Ivonne
dc.contributor.authorMoroni, Paolo
dc.contributor.authorJørgensen, Hannah J
dc.contributor.authorde Lencastre, Hermínia
dc.contributor.authorCercenado, Emilia
dc.contributor.authorGarcía-Garrote, Fernando
dc.contributor.authorBörjesson, Stefan
dc.contributor.authorHæggman, Sara
dc.contributor.authorPerreten, Vincent
dc.contributor.authorTeale, Christopher J
dc.contributor.authorWaller, Andrew S
dc.contributor.authorPichon, Bruno
dc.contributor.authorCurran, Martin D
dc.contributor.authorEllington, Matthew J
dc.contributor.authorWelch, John J
dc.contributor.authorPeacock, Sharon J
dc.contributor.authorSeilly, David J
dc.contributor.authorMorgan, Fiona J E
dc.contributor.authorParkhill, Julian
dc.contributor.authorHadjirin, Nazreen F
dc.contributor.authorLindsay, Jodi A
dc.contributor.authorHolden, Matthew T G
dc.contributor.authorEdwards, Giles F
dc.contributor.authorFoster, Geoffrey
dc.contributor.authorPaterson, Gavin K
dc.contributor.authorDidelot, Xavier
dc.contributor.authorHolmes, Mark A
dc.contributor.authorHarrison, Ewan M
dc.contributor.authorLarsen, Anders R
dc.identifier.citationLarsen , J , Raisen , C L , Ba , X , Sadgrove , N J , Padilla-González , G F , Simmonds , M S J , Loncaric , I , Kerschner , H , Apfalter , P , Hartl , R , Deplano , A , Vandendriessche , S , Černá Bolfíková , B , Hulva , P , Arendrup , M C , Hare , R K , Barnadas , C , Stegger , M , Sieber , R N , Skov , R L , Petersen , A , Angen , Ø , Rasmussen , S L , Espinosa-Gongora , C , Aarestrup , F M , Lindholm , L J , Nykäsenoja , S M , Laurent , F , Becker , K , Walther , B , Kehrenberg , C , Cuny , C , Layer , F , Werner , G , Witte , W , Stamm , I , Moroni , P , Jørgensen , H J , de Lencastre , H , Cercenado , E , García-Garrote , F , Börjesson , S , Hæggman , S , Perreten , V , Teale , C J , Waller , A S , Pichon , B , Curran , M D , Ellington , M J , Welch , J J , Peacock , S J , Seilly , D J , Morgan , F J E , Parkhill , J , Hadjirin , N F , Lindsay , J A , Holden , M T G , Edwards , G F , Foster , G , Paterson , G K , Didelot , X , Holmes , M A , Harrison , E M & Larsen , A R 2022 , ' Emergence of methicillin resistance predates the clinical use of antibiotics ' , Nature , vol. 602 , no. 7895 , pp. 135-141 .
dc.identifier.otherPURE: 277405712
dc.identifier.otherPURE UUID: 12ffad28-ea5c-4411-bd29-ab4822a441cc
dc.identifier.otherPubMed: 34987223
dc.identifier.otherORCID: /0000-0002-4958-2166/work/106397586
dc.identifier.otherScopus: 85122332898
dc.identifier.otherWOS: 000739283800005
dc.descriptionX.D. was funded by a grant from the National Institute for Health Research (NIHR) Health Protection Research Unit in Genomics and Enabling Data (no. NIHR200892). M.A.H. was supported by grants from the Medical Research Council (nos. G1001787/1, MR/N002660/1 and MR/P007201/1) and the Economic and Social Research Council (no. ES/S000186/1). E.M.H. was supported by a UK Research and Innovation (UKRI) Fellowship (no. MR/S00291X/1).en
dc.description.abstractThe 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 antibiotics1. 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.
dc.rightsCopyright © 2022, The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.subjectQR Microbiologyen
dc.titleEmergence of methicillin resistance predates the clinical use of antibioticsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. St Andrews Bioinformatics Uniten
dc.contributor.institutionUniversity of St Andrews. Infection and Global Health Divisionen
dc.description.statusPeer revieweden

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