Larsen, JesperJesperLarsenRaisen, Claire LClaire LRaisenBa, XiaoliangXiaoliangBaSadgrove, Nicholas JNicholas JSadgrovePadilla-González, Guillermo FGuillermo FPadilla-GonzálezSimmonds, Monique S JMonique S JSimmondsLoncaric, IgorIgorLoncaricKerschner, HeidrunHeidrunKerschnerApfalter, PetraPetraApfalterHartl, RainerRainerHartlDeplano, ArianeArianeDeplanoVandendriessche, StienStienVandendriesscheČerná Bolfíková, BarboraBarboraČerná BolfíkováHulva, PavelPavelHulvaArendrup, Maiken CMaiken CArendrupHare, Rasmus KRasmus KHareBarnadas, CélineCélineBarnadasStegger, MarcMarcSteggerSieber, Raphael NRaphael NSieberSkov, Robert LRobert LSkovPetersen, AndreasAndreasPetersenAngen, ØysteinØysteinAngenRasmussen, Sophie LSophie LRasmussenEspinosa-Gongora, CarmenCarmenEspinosa-GongoraAarestrup, Frank MFrank MAarestrupLindholm, Laura JLaura JLindholmNykäsenoja, Suvi MSuvi MNykäsenojaLaurent, FredericFredericLaurentBecker, KarstenKarstenBeckerWalther, BirgitBirgitWaltherKehrenberg, CorinnaCorinnaKehrenbergCuny, ChristianeChristianeCunyLayer, FranziskaFranziskaLayerWerner, GuidoGuidoWernerWitte, WolfgangWolfgangWitteStamm, IvonneIvonneStammMoroni, PaoloPaoloMoroniJørgensen, Hannah JHannah JJørgensende Lencastre, HermíniaHermíniade LencastreCercenado, EmiliaEmiliaCercenadoGarcía-Garrote, FernandoFernandoGarcía-GarroteBörjesson, StefanStefanBörjessonHæggman, SaraSaraHæggmanPerreten, VincentVincentPerreten0000-0001-5722-9445Teale, Christopher JChristopher JTealeWaller, Andrew SAndrew SWallerPichon, BrunoBrunoPichonCurran, Martin DMartin DCurranEllington, Matthew JMatthew JEllingtonWelch, John JJohn JWelchPeacock, Sharon JSharon JPeacockSeilly, David JDavid JSeillyMorgan, Fiona J EFiona J EMorganParkhill, JulianJulianParkhillHadjirin, Nazreen FNazreen FHadjirinLindsay, Jodi AJodi ALindsayHolden, Matthew T GMatthew T GHoldenEdwards, Giles FGiles FEdwardsFoster, GeoffreyGeoffreyFosterPaterson, Gavin KGavin KPatersonDidelot, XavierXavierDidelotHolmes, Mark AMark AHolmesHarrison, Ewan MEwan MHarrisonLarsen, Anders RAnders RLarsen2025-01-082025-01-082022-01-05https://boris-portal.unibe.ch/handle/20.500.12422/201813The 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.en500 - Science::570 - Life sciences; biology600 - Technology::630 - Agriculturearticle10.48350/1652173498722310.1038/s41586-021-04265-w