Antibiotic resistance is a priority public health problem resulting from eco-evolutionary dynamics within microbial communities and their interaction at a mammalian host interface or geographical scale. The links between mammalian host genetics, bacterial gut community, and antimicrobial resistance gene (ARG) content must be better understood in natural populations inhabiting heterogeneous environments. Hybridization, the interbreeding of genetically divergent populations, influences different components of the gut microbial communities. However, its impact on bacterial traits such as antibiotic resistance is unknown. Here, we present that hybridization might shape bacterial communities and ARG occurrence. We used amplicon sequencing to study the gut microbiome and to predict ARG composition in natural populations of house mice (Mus musculus). We compared gastrointestinal bacterial and ARG diversity, composition, and abundance across a gradient of pure and hybrid genotypes in the European House Mouse Hybrid Zone. We observed an increased overall predicted richness of ARG in hybrid mice. We found bacteria-ARG interactions by their co-abundance and detected phenotypes of extreme abundances in hybrid mice at the level of specific bacterial taxa and ARGs, mainly multidrug resistance genes. Our work suggests that mammalian host genetic variation impacts the gut microbiome and chromosomal ARGs. However, it raises further questions on how the mammalian host genetics impact ARGs via microbiome dynamics or environmental covariates.

Centre for Antibiotic Resistance Research in Gothenburg Sweden

Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Experimental and Clinical Research Center Lindenberger Weg 80 13125 Berlin Germany

Department of Infectious Diseases Institute of Biomedicine The Sahlgrenska Academy University of Gothenburg SE 413 46 Gothenburg Sweden

Department of Molecular Parasitology Institute for Biology Humboldt University Berlin Philippstr 13 Haus 14 10115 Berlin Germany

Division of Computational Systems Biology Center for Microbiology and Ecological System Science University of Vienna Djerassipl 1 1030 Vienna Austria

Division of Systems and Synthetic Biology Department of Life Sciences SciLifeLab Chalmers University of Technology Kemivägen 10 SE 412 96 Gothenburg Sweden

Experimental and Clinical Research Center a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité Universitätsmedizin Berlin Germany

German Centre for Cardiovascular Research Partner Site Berlin Berlin Germany

Institute of Ecology Technische Universität Berlin Rothenburgstr 12 12165 Berlin Germany

Laboratory of Mammalian Evolutionary Genetics Institute of Animal Physiology and Genetics Czech Academy of Sciences Veveri 97 60200 Brno Czech Republic

Leibniz Institute for Zoo and Wildlife Research Alfred Kowalke Straße 17 10315 Berlin Germany

Max Delbrück Center for Molecular Medicine in the Helmholtz Association Robert Rössle Str 10 13125 Berlin Germany

Research Facility Studenec Institute of Vertebrate Biology Czech Academy of Sciences Květná 8 60365 Brno Czech Republic

Zobrazit více v PubMed

Medina MJO, Legido-Quigley H, Hsu LY. Antimicrobial resistance in one health. In: Masys A.J., Izurieta R., Reina Ortiz M. (eds.), Global Health Security. Cham: Springer International Publishing, 2020, 209–29https://link.springer.com/http://dx.doi.org/10.1007/978-3-030-23491-1_10 DOI

Larsen J, Raisen CL, Ba Xet al. . Emergence of methicillin resistance predates the clinical use of antibiotics. Nature 2022;602:135–41. 10.1038/s41586-021-04265-w PubMed DOI PMC

Youngblut ND, Reischer GH, Walters Wet al. . Host diet and evolutionary history explain different aspects of gut microbiome diversity among vertebrate clades. Nat Commun 2019;10:2200. 10.1038/s41467-019-10191-3 PubMed DOI PMC

Williams SH, Che X, Paulick Aet al. . New York City house mice (Mus musculus) as potential reservoirs for pathogenic bacteria and antimicrobial resistance determinants. mBio 2018;9:e00624–18. 10.1128/mBio.00624-18 PubMed DOI PMC

Bendová B, Mikula O, Vošlajerová Bímová Bet al. . Divergent gut microbiota in two closely related house mouse subspecies under common garden conditions. FEMS Microbiol Ecol 2022;98:fiac078. 10.1093/femsec/fiac078 PubMed DOI

Baird SJE, Macholán M. What can the Mus musculus musculus/M. m. domesticus hybrid zone tell us about speciation? In: Macholán M., Baird S.J.E., Munclinger P.et al. (eds.), Evolution of the House Mouse. Cambridge: Cambridge University Press, 2012, 334–72(Cambridge Studies in Morphology and Molecules: New Paradigms in Evolutionary Bio)

Baird SJE, Ribas A, Macholán Met al. . Where are the wormy mice? A reexamination of hybrid parasitism in the European house mice hybrid zone. Evolution 2012;66:2757–72. 10.1111/j.1558-5646.2012.01633.x PubMed DOI

Balard A, Jarquín-Díaz VH, Jost Jet al. . Intensity of infection with intracellular Eimeria spp. and pinworms is reduced in hybrid mice compared to parental subspecies. J Evol Biol 2020;33:435–48. 10.1111/jeb.13578 PubMed DOI

Čížková D, Baird SJE, Těšíková Jet al. . Host subspecific viral strains in European house mice: murine cytomegalovirus in the Eastern (Mus musculus musculus) and Western house mouse (Mus musculus domesticus). Virology 2018;521:92–8. 10.1016/j.virol.2018.05.023 PubMed DOI

Wang J, Kalyan S, Steck Net al. . Analysis of intestinal microbiota in hybrid house mice reveals evolutionary divergence in a vertebrate hologenome. Nat Commun 2015;6:6440. 10.1038/ncomms7440 PubMed DOI PMC

Ferreira SC, Jarquín-Díaz VH, Planillo Aet al. . Subspecies divergence, hybridisation and the spatial environment shape phylosymbiosis in the microbiome of house mice. bioRxiv2023;2023–12. 10.1101/2023.12.11.571054 DOI

Doms S, Fokt H, Rühlemann MCet al. . Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice. eLife 2022;11:e75419. 10.7554/eLife.75419 PubMed DOI PMC

Douglas GM, Maffei VJ, Zaneveld JRet al. . PICRUSt2 for prediction of metagenome functions. Nat Biotechnol 2020;38:685–8. 10.1038/s41587-020-0548-6 PubMed DOI PMC

Abramova A, Berendonk TU, Bengtsson-Palme J. A global baseline for qPCR-determined antimicrobial resistance gene prevalence across environments. Environ Int 2023;178:108084. 10.1016/j.envint.2023.108084 PubMed DOI

Klümper U, Recker M, Zhang Let al. . Selection for antimicrobial resistance is reduced when embedded in a natural microbial community. ISME J 2019;13:2927–37. 10.1038/s41396-019-0483-z PubMed DOI PMC

Brooks LE, Ul-Hasan S, Chan BKet al. . Quantifying the evolutionary conservation of genes encoding multidrug efflux pumps in the ESKAPE pathogens to identify antimicrobial drug targets. Msystems 2018;3:10–128. 10.1128/mSystems.00024-18 PubMed DOI PMC

Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med 2007;39:162–76. 10.1080/07853890701195262 PubMed DOI

Alonso A, Morales G, Escalante Ret al. . Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology. J Antimicrob Chemother 2004;53:432–4. 10.1093/jac/dkh074 PubMed DOI

Fackelmann G, Pham CK, Rodríguez Yet al. . Current levels of microplastic pollution impact wild seabird gut microbiomes. Nat Ecol Evol 2023;7:698–706. 10.1038/s41559-023-02013-z PubMed DOI PMC

Papkou A, Hedge J, Kapel Net al. . Efflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates. Nat Commun 2020;11:3970. 10.1038/s41467-020-17735-y PubMed DOI PMC

Laws M, Jin P, Rahman KM. Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends Microbiol 2022;30:57–68. 10.1016/j.tim.2021.05.001 PubMed DOI

Toole DR, Zhao J, Martens-Habbena Wet al. . Bacterial functional prediction tools detect but underestimate metabolic diversity compared to shotgun metagenomics in southwest Florida soils. Appl Soil Ecol 2021;168:104129. 10.1016/j.apsoil.2021.104129 DOI

Eco-evolutionary dynamics of host-microbiome interactions in a natural population of closely related mouse subspecies and their hybrids