Emergence of methicillin resistance predates the clinical use of antibiotics.

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cam.issuedOnline2022-01-05
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 SJ
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 JE
dc.contributor.authorParkhill, Julian
dc.contributor.authorHadjirin, Nazreen F
dc.contributor.authorLindsay, Jodi A
dc.contributor.authorHolden, Matthew TG
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.contributor.orcidLarsen, Jesper [0000-0003-0582-0457]
dc.contributor.orcidBa, Xiaoliang [0000-0002-3882-3585]
dc.contributor.orcidPadilla-González, Guillermo F [0000-0002-8300-6891]
dc.contributor.orcidČerná Bolfíková, Barbora [0000-0001-8059-4889]
dc.contributor.orcidSkov, Robert L [0000-0002-6079-5381]
dc.contributor.orcidRasmussen, Sophie L [0000-0002-2975-678X]
dc.contributor.orcidEspinosa-Gongora, Carmen [0000-0002-9536-0548]
dc.contributor.orcidAarestrup, Frank M [0000-0002-7116-2723]
dc.contributor.orcidBecker, Karsten [0000-0002-6391-1341]
dc.contributor.orcidLayer, Franziska [0000-0002-4613-6478]
dc.contributor.orcidMoroni, Paolo [0000-0002-0974-3084]
dc.contributor.orcidJørgensen, Hannah J [0000-0002-1788-9219]
dc.contributor.orcidde Lencastre, Hermínia [0000-0001-6816-8932]
dc.contributor.orcidCercenado, Emilia [0000-0002-5279-3773]
dc.contributor.orcidBörjesson, Stefan [0000-0003-2219-2659]
dc.contributor.orcidWaller, Andrew S [0000-0002-7111-9549]
dc.contributor.orcidPeacock, Sharon J [0000-0002-1718-2782]
dc.contributor.orcidParkhill, Julian [0000-0002-7069-5958]
dc.contributor.orcidHolden, Matthew TG [0000-0002-4958-2166]
dc.contributor.orcidFoster, Geoffrey [0000-0002-5527-758X]
dc.contributor.orcidPaterson, Gavin K [0000-0002-1880-0095]
dc.contributor.orcidDidelot, Xavier [0000-0003-1885-500X]
dc.contributor.orcidHolmes, Mark A [0000-0002-5454-1625]
dc.contributor.orcidHarrison, Ewan M [0000-0003-2720-0507]
dc.date.accessioned2022-02-24T16:06:18Z
dc.date.available2022-02-24T16:06:18Z
dc.date.issued2022-02
dc.date.submitted2021-05-12
dc.date.updated2022-02-24T16:06:17Z
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.identifier.doi10.17863/CAM.81839
dc.identifier.eissn1476-4687
dc.identifier.issn0028-0836
dc.identifier.others41586-021-04265-w
dc.identifier.other4265
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334424
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41586-021-04265-w
dc.subjectAnimals
dc.subjectAnti-Bacterial Agents
dc.subjectArthrodermataceae
dc.subjectDenmark
dc.subjectEurope
dc.subjectEvolution, Molecular
dc.subjectGeographic Mapping
dc.subjectHedgehogs
dc.subjectHistory, 20th Century
dc.subjectHumans
dc.subjectMethicillin Resistance
dc.subjectMethicillin-Resistant Staphylococcus aureus
dc.subjectNew Zealand
dc.subjectOne Health
dc.subjectPenicillins
dc.subjectPhylogeny
dc.subjectSelection, Genetic
dc.subjectbeta-Lactams
dc.titleEmergence of methicillin resistance predates the clinical use of antibiotics.
dc.typeArticle
dcterms.dateAccepted2021-11-18
prism.endingPage141
prism.issueIdentifier7895
prism.publicationNameNature
prism.startingPage135
prism.volume602
pubs.funder-project-idMedical Research Council (G1001787)
pubs.funder-project-idMedical Research Council (MR/N002660/1)
pubs.funder-project-idMedical Research Council (MR/P007201/1)
pubs.funder-project-idEconomic and Social Research Council (ES/S000186/1)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41586-021-04265-w
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