**Antimicrobial Resistance Collaborators.** 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. *Lancet* **399**:629–655. DOI: https://doi.org/10.1016/S0140-6736(21)02724-0, PMID: 35065702

Bandelt HJ, Forster P, Röhl A. 1999. Median-joining networks for inferring intraspecific phylogenies. *Molecular Biology and Evolution* **16**:37–48. DOI: https://doi.org/10.1093/oxfordjournals.molbev.a026036, PMID: 10331250

Baquero F, Alvarez-Ortega C, Martinez JL. 2009. Ecology and evolution of antibiotic resistance. *Environmental Microbiology Reports* **1**:469–476. DOI: https://doi.org/10.1111/j.1758-2229.2009.00053.x, PMID: 23765924

Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. 2014. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. *BMC Infectious Diseases* **14**:1–25. DOI: https://doi.org/10.1186/1471-2334-14-13

Bengtsson-Palme J, Kristiansson E, Larsson DGJ. 2018. Environmental factors influencing the development and spread of antibiotic resistance. *FEMS Microbiology Reviews* **42**:68–80. DOI: https://doi.org/10.1093/femsre/fux053, PMID: 29069382

Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F, Bürgmann H, Sørum H, Norström M, Pons MN, Kreuzinger N, Huovinen P, Stefani S, Schwartz T, Kisand V, Baquero F, Martinez JL. 2015. Tackling antibiotic resistance: the environmental framework. *Nature Reviews. Microbiology* **13**:310–317. DOI: https://doi.org/10.1038/nrmicro3439, PMID: 25817583

Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. 2015. Molecular mechanisms of antibiotic resistance. *Nature Reviews. Microbiology* **13**:42–51. DOI: https://doi.org/10.1038/nrmicro3380, PMID: 25435309

Blanquart F, Lehtinen S, Fraser C. 2017. An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to streptococcus pneumoniae. *Proceedings. Biological Sciences* **284**:20170679. DOI: https://doi.org/10.1098/rspb.2017.0679, PMID: 28566489

Blondel VD, Guillaume JL, Lambiotte R, Lefebvre E. 2008. Fast unfolding of communities in large networks. *Journal of Statistical Mechanics* **2008**:10008. DOI: https://doi.org/10.1088/1742-5468/2008/10/P10008

Bryant JA, Lamanna C, Morlon H, Kerkhoff AJ, Enquist BJ, Green JL. 2008. Microbes on mountainsides: contrasting elevational patterns of bacterial and plant diversity. *PNAS* **105**:11505–11511. DOI: https://doi.org/10.1073/pnas.0801920105, PMID: 18695215

Burnham KP, Anderson DR. 2002. Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach. New York: Springer. DOI: https://doi.org/10.1007/b97636

Cairns J, Ruokolainen L, Hultman J, Tamminen M, Virta M, Hiltunen T. 2018. Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes. *Communications Biology* **1**:35. DOI: https://doi.org/10.1038/s42003-018-0041-7, PMID: 30271921

Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL. 2009. BLAST: architecture and applications. *BMC Bioinformatics* **10**:1–9. DOI: https://doi.org/10.1186/1471-2105-10-421, PMID: 20003500

Chaumeil PA, Mussig AJ, Hugenholtz P, Parks DH. 2020. GTDB-tk: a toolkit to classify genomes with the genome taxonomy database. *Bioinformatics* **36**:1925–1927. DOI: https://doi.org/10.1093/bioinformatics/btz848, PMID: 31730192

Corel E, Méheust R, Watson AK, McInerney JO, Lopez P, Bapteste E. 2018. Bipartite network analysis of gene sharings in the microbial world. *Molecular Biology and Evolution* **35**:899–913. DOI: https://doi.org/10.1093/molbev/msy001, PMID: 29346651

Cuadrat RRC, Sorokina M, Andrade BG, Goris T, Dávila AMR. 2020. Global ocean resistome revealed: exploring antibiotic resistance gene abundance and distribution in tara oceans samples. *GigaScience* **9**:1–12. DOI: https://doi.org/10.1093/gigascience/giaa046, PMID: 32391909

Cury J, Jové T, Touchon M, Néron B, Rocha EP. 2016. Identification and analysis of integrons and cassette arrays in bacterial genomes. *Nucleic Acids Research* **44**:4539–4550. DOI: https://doi.org/10.1093/nar/gkw319, PMID: 27130947

Czekalski N, Sigdel R, Birtel J, Matthews B, Bürgmann H. 2015. Does human activity impact the natural antibiotic resistance background? abundance of antibiotic resistance genes in 21 Swiss lakes. *Environment International* **81**:45–55. DOI: https://doi.org/10.1016/j.envint.2015.04.005, PMID: 25913323

Danner MC, Robertson A, Behrends V, Reiss J. 2019. Antibiotic pollution in surface fresh waters: occurrence and effects. *The Science of the Total Environment* **664**:793–804. DOI: https://doi.org/10.1016/j.scitotenv.2019.01.046, PMID: 30763859

Davies JE. 1983. Resistance to aminoglycosides: mechanisms and frequency. *Clinical Infectious Diseases* **5**:S261–S267. DOI: https://doi.org/10.1093/clinids/5.Supplement_2.S261

D'Costa VM, King CE, Kalan L, Morar M, Sung WWL, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. 2011. Antibiotic resistance is ancient. *Nature* **477**:457–461. DOI: https://doi.org/10.1038/nature10388, PMID: 21881561

Depardieu F, Podglajen I, Leclercq R, Collatz E, Courvalin P. 2007. Modes and modulations of antibiotic resistance gene expression. *Clinical Microbiology Reviews* **20**:79–114. DOI: https://doi.org/10.1128/CMR.00015-06, PMID: 17223624

Durand GA, Raoult D, Dubourg G. 2019. Antibiotic discovery: history, methods and perspectives. *International Journal of Antimicrobial Agents* **53**:371–382. DOI: https://doi.org/10.1016/j.ijantimicag.2018.11.010, PMID: 30472287
**Antimicrobial Resistance Collaborators.** 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. *Lancet* **399**:629–655. DOI: https://doi.org/10.1016/S0140-6736(21)02724-0, PMID: 35065702

Bandelt HJ, Forster P, Röhl A. 1999. Median-joining networks for inferring intraspecific phylogenies. *Molecular Biology and Evolution* **16**:37–48. DOI: https://doi.org/10.1093/oxfordjournals.molbev.a026036, PMID: 10331250

Baquero F, Alvarez-Ortega C, Martinez JL. 2009. Ecology and evolution of antibiotic resistance. *Environmental Microbiology Reports* **1**:469–476. DOI: https://doi.org/10.1111/j.1758-2229.2009.00053.x, PMID: 23765924

Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. 2014. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. *BMC Infectious Diseases* **14**:1–25. DOI: https://doi.org/10.1186/1471-2334-14-13

Bengtsson-Palme J, Kristiansson E, Larsson DGJ. 2018. Environmental factors influencing the development and spread of antibiotic resistance. *FEMS Microbiology Reviews* **42**:68–80. DOI: https://doi.org/10.1093/femsre/fux053, PMID: 29069382

Berendonk TU, Manaia CM, Merlin C, Fatta-Kassinos D, Cytryn E, Walsh F, Bürgmann H, Sørum H, Norström M, Pons MN, Kreuzinger N, Huovinen P, Stefani S, Schwartz T, Kisand V, Baquero F, Martinez JL. 2015. Tackling antibiotic resistance: the environmental framework. *Nature Reviews. Microbiology* **13**:310–317. DOI: https://doi.org/10.1038/nrmicro3439, PMID: 25817583

Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. 2015. Molecular mechanisms of antibiotic resistance. *Nature Reviews. Microbiology* **13**:42–51. DOI: https://doi.org/10.1038/nrmicro3380, PMID: 25435309

Blanquart F, Lehtinen S, Fraser C. 2017. An evolutionary model to predict the frequency of antibiotic resistance under seasonal antibiotic use, and an application to streptococcus pneumoniae. *Proceedings. Biological Sciences* **284**:20170679. DOI: https://doi.org/10.1098/rspb.2017.0679, PMID: 28566489

Blondel VD, Guillaume JL, Lambiotte R, Lefebvre E. 2008. Fast unfolding of communities in large networks. *Journal of Statistical Mechanics* **2008**:10008. DOI: https://doi.org/10.1088/1742-5468/2008/10/P10008

Bryant JA, Lamanna C, Morlon H, Kerkhoff AJ, Enquist BJ, Green JL. 2008. Microbes on mountainsides: contrasting elevational patterns of bacterial and plant diversity. *PNAS* **105**:11505–11511. DOI: https://doi.org/10.1073/pnas.0801920105, PMID: 18695215

Burnham KP, Anderson DR. 2002. Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach. New York: Springer. DOI: https://doi.org/10.1007/b97636

Cairns J, Ruokolainen L, Hultman J, Tamminen M, Virta M, Hiltunen T. 2018. Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes. *Communications Biology* **1**:35. DOI: https://doi.org/10.1038/s42003-018-0041-7, PMID: 30271921

Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL. 2009. BLAST: architecture and applications. *BMC Bioinformatics* **10**:1–9. DOI: https://doi.org/10.1186/1471-2105-10-421, PMID: 20003500

Chaumeil PA, Mussig AJ, Hugenholtz P, Parks DH. 2020. GTDB-tk: a toolkit to classify genomes with the genome taxonomy database. *Bioinformatics* **36**:1925–1927. DOI: https://doi.org/10.1093/bioinformatics/btz848, PMID: 31730192

Corel E, Méheust R, Watson AK, McInerney JO, Lopez P, Bapteste E. 2018. Bipartite network analysis of gene sharings in the microbial world. *Molecular Biology and Evolution* **35**:899–913. DOI: https://doi.org/10.1093/molbev/msy001, PMID: 29346651

Cuadrat RRC, Sorokina M, Andrade BG, Goris T, Dávila AMR. 2020. Global ocean resistome revealed: exploring antibiotic resistance gene abundance and distribution in tara oceans samples. *GigaScience* **9**:1–12. DOI: https://doi.org/10.1093/gigascience/giaa046, PMID: 32391909

Cury J, Jové T, Touchon M, Néron B, Rocha EP. 2016. Identification and analysis of integrons and cassette arrays in bacterial genomes. *Nucleic Acids Research* **44**:4539–4550. DOI: https://doi.org/10.1093/nar/gkw319, PMID: 27130947

Czekalski N, Sigdel R, Birtel J, Matthews B, Bürgmann H. 2015. Does human activity impact the natural antibiotic resistance background? abundance of antibiotic resistance genes in 21 Swiss lakes. *Environment International* **81**:45–55. DOI: https://doi.org/10.1016/j.envint.2015.04.005, PMID: 25913323

Danner MC, Robertson A, Behrends V, Reiss J. 2019. Antibiotic pollution in surface fresh waters: occurrence and effects. *The Science of the Total Environment* **664**:793–804. DOI: https://doi.org/10.1016/j.scitotenv.2019.01.046, PMID: 30763859

Davies JE. 1983. Resistance to aminoglycosides: mechanisms and frequency. *Clinical Infectious Diseases* **5**:S261–S267. DOI: https://doi.org/10.1093/clinids/5.Supplement_2.S261

D'Costa VM, King CE, Kalan L, Morar M, Sung WWL, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. 2011. Antibiotic resistance is ancient. *Nature* **477**:457–461. DOI: https://doi.org/10.1038/nature10388, PMID: 21881561

Depardieu F, Podglajen I, Leclercq R, Collatz E, Courvalin P. 2007. Modes and modulations of antibiotic resistance gene expression. *Clinical Microbiology Reviews* **20**:79–114. DOI: https://doi.org/10.1128/CMR.00015-06, PMID: 17223624

Durand GA, Raoult D, Dubourg G. 2019. Antibiotic discovery: history, methods and perspectives. *International Journal of Antimicrobial Agents* **53**:371–382. DOI: https://doi.org/10.1016/j.ijantimicag.2018.11.010, PMID: 30472287
Eddy SR. 2011. Accelerated profile HMM searches. *PLOS Computational Biology* **7:e1002195**. DOI: https://doi.org/10.1371/journal.pcbi.1002195, PMID: 22039361

Eltai NO, Yassine HM, El-Obeid T, Al-Hadidi SH, Al Thani AA, Alali WQ. 2020. Prevalence of antibiotic-resistant *Escherichia coli* isolates from local and imported retail chicken carcasses. *Journal of Food Protection* **83:2200–2208**. DOI: https://doi.org/10.4315/JFP-20-113, PMID: 32730573

Enne VI, Bennett PM, Livermore DM, Hall LMC. 2004. Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure. *The Journal of Antimicrobial Chemotherapy* **53:958–963**. DOI: https://doi.org/10.1093/jac/dkh217, PMID: 15102746

European Centre for Disease Prevention and Control. 2021. Antimicrobial consumption database (ESAC-Net). https://www.ecdc.europa.eu/en/antimicrobial-consumption/surveillance-and-disease-data/database [Accessed November 23, 2021].

European Medicines Agency. 2019. Sales of veterinary antimicrobial agents in 31 European countries in 2017. European Medicines Agency. https://www.ema.europa.eu/en/documents/report/sales-veterinary-antimicrobial-agents-31-european-countries-2017_en.pdf

European Medicines Agency. 2021. European database of sales of veterinary antimicrobial agents. https://esvaci.ema.europa.eu/analytics/saw.dll?PortalPages [Accessed November 24, 2021].

Eurostat. 2022. Eurostat Data Brower – Animal Production. https://ec.europa.eu/eurostat/datab browser/explore/ all/agric?subtheme=agr.apro.apro_anip [Accessed July 1, 2021].

Faith DP. 1992. Conservation evaluation and phylogenetic diversity. *Biological Conservation* **61:1–10**. DOI: https://doi.org/10.1016/0006-3207(92)91201-3

Feldgarden M, Brover V, Haft DH, Prasad AB, Slotta DJ, Tolstoy I, Tyson GH, Zhao S, Hsu C-H, McDermott PF, Tadesse DA, Morales C, Simmons M, Tillman G, Wasilenko J, Folster JP, Klimke W. 2019. Validating the amrfinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates. *Antimicrobial Agents and Chemotherapy* **63:e00483-19**. DOI: https://doi.org/10.1128/AAC.00483-19, PMID: 31427293

Finken M, Kirschner P, Meier A, Wrede A, Böttger EC. 1993. Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. *Molecular Microbiology* **9:1239–1246**. DOI: https://doi.org/10.1111/j.1365-2958.1993.tb01253.x, PMID: 7934937

Forsberg KJ, Reyes A, Wang B, Selleck EM, Sommer MOA, Dantas G. 2012. The shared antibiotic resistome of soil bacteria and human pathogens. *Science* **337:1107–1111**. DOI: https://doi.org/10.1126/science.1220761, PMID: 22936781

Forsberg KJ, Patel S, Gibson MK, Lauber CL, Knight R, Fierer N, Dantas G. 2014. Bacterial phylogeny structures soil resistomes across habitats. *Nature* **509:612–616**. DOI: https://doi.org/10.1038/nature13377, PMID: 24847883

Founou LL, Founou RC, Essack SY. 2016. Antibiotic resistance in the food chain: a developing country-perspective. *Frontiers in Microbiology* **7:1881**. DOI: https://doi.org/10.3389/fmicb.2016.01881, PMID: 27933044

Garneau-Tsodikova S, Labby KJ. 2016. Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. *MedChemComm* **7:11–27**. DOI: https://doi.org/10.1039/C5MD00344J, PMID: 26877861

Gibson MK, Forsberg KJ, Dantas G. 2014. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology. *The ISME Journal* **9:207–216**. DOI: https://doi.org/10.1038/ismej.2014.106, PMID: 25003965

Girgis HZ. 2015. Red: an intelligent, rapid, accurate tool for detecting repeats de-novo on the genomic scale. *BMC Bioinformatics* **16:1–19**. DOI: https://doi.org/10.1186/s12859-015-0654-5

Goerner-Potvin P, Bourque G. 2018. Computational tools to unmask transposable elements. *Nature Reviews. Genetics* **19:688–704**. DOI: https://doi.org/10.1038/s41576-018-0050-x, PMID: 30232369

Goossens H, Ferech M, Vander Stichele R, Elseviers M, ESAC Project Group. 2005. Outpatient antibiotic use in europe and association with resistance: a cross-national database study. *Lancet* **365:579–587**. DOI: https://doi.org/10.1016/S0140-6736(05)17907-0, PMID: 15708101

Gothwal R, Shashidhar T. 2015. Antibiotic pollution in the environment: a review. *CLEAN - Soil, Air, Water* **43:479–489**. DOI: https://doi.org/10.1002/clen.201300989

Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, Andersson DI. 2011. Selection of resistant bacteria at very low antibiotic concentrations. *PLOS Pathogens* **7:e1002158**. DOI: https://doi.org/10.1371/journal.ppat.1002158, PMID: 21811410

Hernando-Amado S, Coque TM, Baquero F, Martínez JL. 2019. Defining and combating antibiotic resistance from one health and global health perspectives. *Nature Microbiology* **4:1432–1442**. DOI: https://doi.org/10.1038/s41564-019-0503-9, PMID: 31439928

Holmes AH, Moore LSP, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJV. 2016. Understanding the mechanisms and drivers of antimicrobial resistance. *Lancet* **387:176–187**. DOI: https://doi.org/10.1016/S0140-6736(15)00473-0, PMID: 26603922

Hughes D, Andersson DI. 2017. Evolutionary trajectories to antibiotic resistance. *Annual Review of Microbiology* **71:579–596**. DOI: https://doi.org/10.1146/annurev-micro-090816-093813, PMID: 28697667

Jana S, Deb JK. 2006. Molecular understanding of aminoglycoside action and resistance. *Applied Microbiology and Biotechnology* **70:140–150**. DOI: https://doi.org/10.1007/s00253-005-0279-0, PMID: 16391922
Eddy SR. 2011. Accelerated profile HMM searches. *PLOS Computational Biology* **7:e1002195**. DOI: https://doi.org/10.1371/journal.pcbi.1002195, PMID: 22039361

Eltai NO, Yassine HM, El-Obeid T, Al-Hadidi SH, Al Thani AA, Alali WQ. 2020. Prevalence of antibiotic-resistant *Escherichia coli* isolates from local and imported retail chicken carcasses. *Journal of Food Protection* **83:2200–2208**. DOI: https://doi.org/10.4315/JFP-20-113, PMID: 32730573

Enne VI, Bennett PM, Livermore DM, Hall LMC. 2004. Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure. *The Journal of Antimicrobial Chemotherapy* **53:958–963**. DOI: https://doi.org/10.1093/jac/dkh217, PMID: 15102746

European Centre for Disease Prevention and Control. 2021. Antimicrobial consumption database (ESAC-Net). https://www.ecdc.europa.eu/en/antimicrobial-consumption/surveillance-and-disease-data/database [Accessed November 23, 2021].

European Medicines Agency. 2019. Sales of veterinary antimicrobial agents in 31 European countries in 2017. European Medicines Agency. https://www.ema.europa.eu/en/documents/report/sales-veterinary-antimicrobial-agents-31-european-countries-2017_en.pdf

European Medicines Agency. 2021. European database of sales of veterinary antimicrobial agents. https://esvaci.ema.europa.eu/analytics/saw.dll?PortalPages [Accessed November 24, 2021].

Eurostat. 2022. Eurostat Data Brower – Animal Production. https://ec.europa.eu/eurostat/datab browser/explore/ all/agric?subtheme=agr.apro.apro_anip [Accessed July 1, 2021].

Faith DP. 1992. Conservation evaluation and phylogenetic diversity. *Biological Conservation* **61:1–10**. DOI: https://doi.org/10.1016/0006-3207(92)91201-3

Feldgarden M, Brover V, Haft DH, Prasad AB, Slotta DJ, Tolstoy I, Tyson GH, Zhao S, Hsu C-H, McDermott PF, Tadesse DA, Morales C, Simmons M, Tillman G, Wasilenko J, Folster JP, Klimke W. 2019. Validating the amrfinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates. *Antimicrobial Agents and Chemotherapy* **63:e00483-19**. DOI: https://doi.org/10.1128/AAC.00483-19, PMID: 31427293

Finken M, Kirschner P, Meier A, Wrede A, Böttger EC. 1993. Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. *Molecular Microbiology* **9:1239–1246**. DOI: https://doi.org/10.1111/j.1365-2958.1993.tb01253.x, PMID: 7934937

Forsberg KJ, Reyes A, Wang B, Selleck EM, Sommer MOA, Dantas G. 2012. The shared antibiotic resistome of soil bacteria and human pathogens. *Science* **337:1107–1111**. DOI: https://doi.org/10.1126/science.1220761, PMID: 22936781

Forsberg KJ, Patel S, Gibson MK, Lauber CL, Knight R, Fierer N, Dantas G. 2014. Bacterial phylogeny structures soil resistomes across habitats. *Nature* **509:612–616**. DOI: https://doi.org/10.1038/nature13377, PMID: 24847883

Founou LL, Founou RC, Essack SY. 2016. Antibiotic resistance in the food chain: a developing country-perspective. *Frontiers in Microbiology* **7:1881**. DOI: https://doi.org/10.3389/fmicb.2016.01881, PMID: 27933044

Garneau-Tsodikova S, Labby KJ. 2016. Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. *MedChemComm* **7:11–27**. DOI: https://doi.org/10.1039/C5MD00344J, PMID: 26877861

Gibson MK, Forsberg KJ, Dantas G. 2014. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology. *The ISME Journal* **9:207–216**. DOI: https://doi.org/10.1038/ismej.2014.106, PMID: 25003965

Girgis HZ. 2015. Red: an intelligent, rapid, accurate tool for detecting repeats de-novo on the genomic scale. *BMC Bioinformatics* **16:1–19**. DOI: https://doi.org/10.1186/s12859-015-0654-5

Goerner-Potvin P, Bourque G. 2018. Computational tools to unmask transposable elements. *Nature Reviews. Genetics* **19:688–704**. DOI: https://doi.org/10.1038/s41576-018-0050-x, PMID: 30232369

Goossens H, Ferech M, Vander Stichele R, Elseviers M, ESAC Project Group. 2005. Outpatient antibiotic use in europe and association with resistance: a cross-national database study. *Lancet* **365:579–587**. DOI: https://doi.org/10.1016/S0140-6736(05)17907-0, PMID: 15708101

Gothwal R, Shashidhar T. 2015. Antibiotic pollution in the environment: a review. *CLEAN - Soil, Air, Water* **43:479–489**. DOI: https://doi.org/10.1002/clen.201300989

Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, Andersson DI. 2011. Selection of resistant bacteria at very low antibiotic concentrations. *PLOS Pathogens* **7:e1002158**. DOI: https://doi.org/10.1371/journal.ppat.1002158, PMID: 21811410

Hernando-Amado S, Coque TM, Baquero F, Martínez JL. 2019. Defining and combating antibiotic resistance from one health and global health perspectives. *Nature Microbiology* **4:1432–1442**. DOI: https://doi.org/10.1038/s41564-019-0503-9, PMID: 31439928

Holmes AH, Moore LSP, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJV. 2016. Understanding the mechanisms and drivers of antimicrobial resistance. *Lancet* **387:176–187**. DOI: https://doi.org/10.1016/S0140-6736(15)00473-0, PMID: 26603922

Hughes D, Andersson DI. 2017. Evolutionary trajectories to antibiotic resistance. *Annual Review of Microbiology* **71:579–596**. DOI: https://doi.org/10.1146/annurev-micro-090816-093813, PMID: 28697667

Jana S, Deb JK. 2006. Molecular understanding of aminoglycoside action and resistance. *Applied Microbiology and Biotechnology* **70:140–150**. DOI: https://doi.org/10.1007/s00253-005-0279-0, PMID: 16391922
Jones P, Binns D, Chang HY, Fraser M, Li W, McAnulla C, McWilliam H, Maslen J, Mitchell A, Nuka G, Pesseat S, Quinn AF, Sangrador-Vegas A, Scheremetjew M, Yong SY, Lopez R, Hunter S. 2014. InterProScan 5: genome-scale protein function classification. *Bioinformatics* **30**:1236–1240. DOI: https://doi.org/10.1093/bioinformatics/btu031, PMID: 24451626

Ju F, Beck K, Yin X, Maccagnan A, McArdell CS, Singer HP, Johnson DR, Zhang T, Bürgmann H. 2019. Wastewater treatment plant resistomes are shaped by bacterial composition, genetic exchange, and upregulated expression in the effluent microbiomes. *The ISME Journal* **13**:346–360. DOI: https://doi.org/10.1038/s41396-018-0277-8, PMID: 30250051

Karkman A, Johnson TA, Lyra C, Stedtfeld RD, Tamminen M, Tiedje JM, Virta M. 2016. High-throughput quantification of antibiotic resistance genes from an urban wastewater treatment plant. *FEMS Microbiology Ecology* **92**:14. DOI: https://doi.org/10.1093/femsec/fiw014, PMID: 26832203

Karkman A, Pärnänen K, Larsson DGJ. 2019. Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments. *Nature Communications* **10**:80. DOI: https://doi.org/10.1038/s41467-018-07992-3, PMID: 30622259

Kime L, Randall CP, Banda FI, Coll F, Wright J, Richardson J, Empel J, Parkhill J, O'Neill AJ. 2019. Transient silencing of antibiotic resistance by mutation represents a significant potential source of unanticipated therapeutic failure. *MBio* **10**:e01755-19. DOI: https://doi.org/10.1128/mBio.01755-19, PMID: 31662453

Kümmerer K, Henninger A. 2003. Promoting resistance by the emission of antibiotics from hospitals and households into effluent. *Clinical Microbiology and Infection* **9**:1203–1214. DOI: https://doi.org/10.1111/j.1469-0691.2003.00739.x, PMID: 14686985

Lobby KJ, Garneau-Tsodikova S. 2013. Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections. *Future Medicinal Chemistry* **5**:1285–1309. DOI: https://doi.org/10.4155/fmc.13.80, PMID: 23859208

Laliberté E, Legendre P, Maintainer BS. 2014. Package "FD" type package title measuring functional diversity (FD) from multiple traits, and other tools for functional ecology. 1.0-12.1. CRAN. https://cran.r-project.org/web/packages/FD/index.html

Lavilla Lerma L, Benomar N, Valenzuela AS, de Casado Muñoz MC, Gálvez A, Abriouel H. 2014. Role of efrab efflux pump in biocide tolerance and antibiotic resistance of enterococcus faecalis and enterococcus faecium isolated from traditional fermented foods and the effect of EDTA as efrab inhibitor. *Food Microbiology* **44**:249–257. DOI: https://doi.org/10.1016/j.fm.2014.06.009, PMID: 25084670

Le Hello S, Hendriksen RS, Doublet B, Fisher I, Nielsen EM, Whichard JM, Bouchrif B, Fashae K, Granier SA, Jourdan-Da Silva N, Cloeckaert A, Threlfall EJ, Angulo FJ, Aarestrup FM, Wain J, Weill FX. 2011. International spread of an epidemic population of *Salmonella enterica* serotype Kentucky ST198 resistant to ciprofloxacin. *The Journal of Infectious Diseases* **204**:675–684. DOI: https://doi.org/10.1093/infdis/jir409, PMID: 21813512

Lepelletier D, Andremont A, Grandbastien B, National Working Group. 2011. Risk of highly resistant bacteria importation from repatriates and travelers hospitalized in foreign countries: about the French recommendations to limit their spread. *Journal of Travel Medicine* **18**:344–351. DOI: https://doi.org/10.1111/j.1708-8305.2011.00547.x, PMID: 21896099

Li J, Zhang H, Chen Y, Luo Y, Zhang H. 2016. Sources identification of antibiotic pollution combining land use information and multivariate statistics. *Environmental Monitoring and Assessment* **188**:1–12. DOI: https://doi.org/10.1007/s10661-016-5439-4, PMID: 27338264

Liu M, Li X, Xie Y, Bi D, Sun J, Li J, Tai C, Deng Z, Ou HY. 2019. ICEberg 2.0: an updated database of bacterial integrative and conjugative elements. *Nucleic Acids Research* **47**:D660–D665. DOI: https://doi.org/10.1093/nar/gky1123, PMID: 30407568

Livermore DM, Blaser M, Carrs O, Cassell G, Fishman N, Guidos R, Levy S, Powers J, Norrby R, Tillotson G, Davies R, Projan S, Dawson M, Monnet D, Keogh-Brown M, Hand K, Garner S, Findlay D, Morel C, Wise R, et al. 2011. Discovery research: the scientific challenge of finding new antibiotics. *The Journal of Antimicrobial Chemotherapy* **66**:1941–1944. DOI: https://doi.org/10.1093/jac/dkr262, PMID: 21700626

Lu H-P, Lai Y-C, Huang S-W, Chen H-C, Hsieh C, Yu H-T. 2014. Spatial heterogeneity of gut microbiota reveals multiple bacterial communities with distinct characteristics. *Scientific Reports* **4**:6185. DOI: https://doi.org/10.1038/srep06185, PMID: 25155166

Marti E, Variatza E, Balcazar JL. 2014. The role of aquatic ecosystems as reservoirs of antibiotic resistance. *Trends in Microbiology* **22**:36–41. DOI: https://doi.org/10.1016/j.tim.2013.11.001, PMID: 24289955

Martínez JL, Coque TM, Baquero F. 2015. Prioritizing risks of antibiotic resistance genes in all metagenomes. *Nature Reviews. Microbiology* **13**:396. DOI: https://doi.org/10.1038/nrmicro3399-c2, PMID: 25915635

Miele V, Penel S, Duret L. 2011. Ultra-Fast sequence clustering from similarity networks with silix. *BMC Bioinformatics* **12**:1–9. DOI: https://doi.org/10.1186/1471-2105-12-116, PMID: 21513511

Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. 1999. Aminoglycosides: activity and resistance. *Antimicrobial Agents and Chemotherapy* **43**:727–737. DOI: https://doi.org/10.1128/AAC.43.4.727, PMID: 10103173

Mölstad S, Erntell M, Hanberger H, Melander E, Norman C, Skoog G, Lundborg CS, Söderström A, Torell E, Cars O. 2008. Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish strama programme. *The Lancet. Infectious Diseases* **8**:125–132. DOI: https://doi.org/10.1016/S1473-3099(08)70017-3, PMID: 18222163

Munck C, Albertsen M, Telke A, Ellabaan M, Nielsen PH, Sommer MOA. 2015. Limited dissemination of the wastewater treatment plant core resistome. *Nature Communications* **6**:8452. DOI: https://doi.org/10.1038/ncomms9452, PMID: 26419330
Jones P, Binns D, Chang HY, Fraser M, Li W, McAnulla C, McWilliam H, Maslen J, Mitchell A, Nuka G, Pesseat S, Quinn AF, Sangrador-Vegas A, Scheremetjew M, Yong SY, Lopez R, Hunter S. 2014. InterProScan 5: genome-scale protein function classification. *Bioinformatics* **30**:1236–1240. DOI: https://doi.org/10.1093/bioinformatics/btu031, PMID: 24451626

Ju F, Beck K, Yin X, Maccagnan A, McArdell CS, Singer HP, Johnson DR, Zhang T, Bürgmann H. 2019. Wastewater treatment plant resistomes are shaped by bacterial composition, genetic exchange, and upregulated expression in the effluent microbiomes. *The ISME Journal* **13**:346–360. DOI: https://doi.org/10.1038/s41396-018-0277-8, PMID: 30250051

Karkman A, Johnson TA, Lyra C, Stedtfeld RD, Tamminen M, Tiedje JM, Virta M. 2016. High-throughput quantification of antibiotic resistance genes from an urban wastewater treatment plant. *FEMS Microbiology Ecology* **92**:14. DOI: https://doi.org/10.1093/femsec/fiw014, PMID: 26832203

Karkman A, Pärnänen K, Larsson DGJ. 2019. Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments. *Nature Communications* **10**:80. DOI: https://doi.org/10.1038/s41467-018-07992-3, PMID: 30622259

Kime L, Randall CP, Banda FI, Coll F, Wright J, Richardson J, Empel J, Parkhill J, O'Neill AJ. 2019. Transient silencing of antibiotic resistance by mutation represents a significant potential source of unanticipated therapeutic failure. *MBio* **10**:e01755-19. DOI: https://doi.org/10.1128/mBio.01755-19, PMID: 31662453

Kümmerer K, Henninger A. 2003. Promoting resistance by the emission of antibiotics from hospitals and households into effluent. *Clinical Microbiology and Infection* **9**:1203–1214. DOI: https://doi.org/10.1111/j.1469-0691.2003.00739.x, PMID: 14686985

Lobby KJ, Garneau-Tsodikova S. 2013. Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections. *Future Medicinal Chemistry* **5**:1285–1309. DOI: https://doi.org/10.4155/fmc.13.80, PMID: 23859208

Laliberté E, Legendre P, Maintainer BS. 2014. Package "FD" type package title measuring functional diversity (FD) from multiple traits, and other tools for functional ecology. 1.0-12.1. CRAN. https://cran.r-project.org/web/packages/FD/index.html

Lavilla Lerma L, Benomar N, Valenzuela AS, de Casado Muñoz MC, Gálvez A, Abriouel H. 2014. Role of efrab efflux pump in biocide tolerance and antibiotic resistance of enterococcus faecalis and enterococcus faecium isolated from traditional fermented foods and the effect of EDTA as efrab inhibitor. *Food Microbiology* **44**:249–257. DOI: https://doi.org/10.1016/j.fm.2014.06.009, PMID: 25084670

Le Hello S, Hendriksen RS, Doublet B, Fisher I, Nielsen EM, Whichard JM, Bouchrif B, Fashae K, Granier SA, Jourdan-Da Silva N, Cloeckaert A, Threlfall EJ, Angulo FJ, Aarestrup FM, Wain J, Weill FX. 2011. International spread of an epidemic population of *Salmonella enterica* serotype Kentucky ST198 resistant to ciprofloxacin. *The Journal of Infectious Diseases* **204**:675–684. DOI: https://doi.org/10.1093/infdis/jir409, PMID: 21813512

Lepelletier D, Andremont A, Grandbastien B, National Working Group. 2011. Risk of highly resistant bacteria importation from repatriates and travelers hospitalized in foreign countries: about the French recommendations to limit their spread. *Journal of Travel Medicine* **18**:344–351. DOI: https://doi.org/10.1111/j.1708-8305.2011.00547.x, PMID: 21896099

Li J, Zhang H, Chen Y, Luo Y, Zhang H. 2016. Sources identification of antibiotic pollution combining land use information and multivariate statistics. *Environmental Monitoring and Assessment* **188**:1–12. DOI: https://doi.org/10.1007/s10661-016-5439-4, PMID: 27338264

Liu M, Li X, Xie Y, Bi D, Sun J, Li J, Tai C, Deng Z, Ou HY. 2019. ICEberg 2.0: an updated database of bacterial integrative and conjugative elements. *Nucleic Acids Research* **47**:D660–D665. DOI: https://doi.org/10.1093/nar/gky1123, PMID: 30407568

Livermore DM, Blaser M, Carrs O, Cassell G, Fishman N, Guidos R, Levy S, Powers J, Norrby R, Tillotson G, Davies R, Projan S, Dawson M, Monnet D, Keogh-Brown M, Hand K, Garner S, Findlay D, Morel C, Wise R, et al. 2011. Discovery research: the scientific challenge of finding new antibiotics. *The Journal of Antimicrobial Chemotherapy* **66**:1941–1944. DOI: https://doi.org/10.1093/jac/dkr262, PMID: 21700626

Lu H-P, Lai Y-C, Huang S-W, Chen H-C, Hsieh C, Yu H-T. 2014. Spatial heterogeneity of gut microbiota reveals multiple bacterial communities with distinct characteristics. *Scientific Reports* **4**:6185. DOI: https://doi.org/10.1038/srep06185, PMID: 25155166

Marti E, Variatza E, Balcazar JL. 2014. The role of aquatic ecosystems as reservoirs of antibiotic resistance. *Trends in Microbiology* **22**:36–41. DOI: https://doi.org/10.1016/j.tim.2013.11.001, PMID: 24289955

Martínez JL, Coque TM, Baquero F. 2015. Prioritizing risks of antibiotic resistance genes in all metagenomes. *Nature Reviews. Microbiology* **13**:396. DOI: https://doi.org/10.1038/nrmicro3399-c2, PMID: 25915635

Miele V, Penel S, Duret L. 2011. Ultra-Fast sequence clustering from similarity networks with silix. *BMC Bioinformatics* **12**:1–9. DOI: https://doi.org/10.1186/1471-2105-12-116, PMID: 21513511

Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. 1999. Aminoglycosides: activity and resistance. *Antimicrobial Agents and Chemotherapy* **43**:727–737. DOI: https://doi.org/10.1128/AAC.43.4.727, PMID: 10103173

Mölstad S, Erntell M, Hanberger H, Melander E, Norman C, Skoog G, Lundborg CS, Söderström A, Torell E, Cars O. 2008. Sustained reduction of antibiotic use and low bacterial resistance: 10-year follow-up of the Swedish strama programme. *The Lancet. Infectious Diseases* **8**:125–132. DOI: https://doi.org/10.1016/S1473-3099(08)70017-3, PMID: 18222163

Munck C, Albertsen M, Telke A, Ellabaan M, Nielsen PH, Sommer MOA. 2015. Limited dissemination of the wastewater treatment plant core resistome. *Nature Communications* **6**:8452. DOI: https://doi.org/10.1038/ncomms9452, PMID: 26419330
Murray BE, Murray B. 1991. New aspects of antimicrobial resistance and the resulting therapeutic dilemmas. *Journal of Infectious Diseases* **163**:1185–1194. DOI: https://doi.org/10.1093/infdis/163.6.1185

Nellums LB, Thompson H, Holmes A, Castro-Sánchez E, Otter JA, Norredam M, Friedland JS, Hargreaves S. 2018. Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis. *The Lancet*. *Infectious Diseases* **18**:796–811. DOI: https://doi.org/10.1016/S1473-3099(18)30219-6, PMID: 29779917

O'Neill J. 2014. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Review on Antimicrobial Resistance.

Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ. 2015. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. *BMC Genomics* **16**:964. DOI: https://doi.org/10.1186/s12864-015-2153-5, PMID: 26576951

Parks DH, Chuvochina M, Waite DW, Rinke C, Skarshewski A, Chaumeil PA, Hugenholtz P. 2018. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. *Nature Biotechnology* **36**:996–1004. DOI: https://doi.org/10.1038/nbt.4229, PMID: 30148503

Pehrsson EC, Tsukayama P, Patel S, Mejía-Bautista M, Sosa-Soto G, Navarrete KM, Calderon M, Cabrera L, Hoyos-Arango W, Bertoli MT, Berg DE, Gilman RH, Dantas G. 2016. Interconnected microbiomes and resistomes in low-income human habitats. *Nature* **533**:212–216. DOI: https://doi.org/10.1038/nature17672, PMID: 27172044

Perron GG, Whyte L, Turnbaugh PJ, Goordial J, Hanage WP, Dantas G, Desai MM. 2015. Functional characterization of bacteria isolated from ancient Arctic soil exposes diverse resistance mechanisms to modern antibiotics. *PLOS ONE* **10**:e0069533. DOI: https://doi.org/10.1371/journal.pone.0069533, PMID: 25807523

Pitta DW, Dou Z, Kumar S, Indugu N, Toth JD, Vecchiarelli B, Bhukya B. 2016. Metagenomic evidence of the prevalence and distribution patterns of antimicrobial resistance genes in dairy agroecosystems. *Foodborne Pathogens and Disease* **13**:296–302. DOI: https://doi.org/10.1089/fpd.2015.2092, PMID: 27046731

Podolsky SH. 2018. The evolving response to antibiotic resistance (1945–2018). *Palgrave Communications* **4**:1–8. DOI: https://doi.org/10.1057/s41599-018-0181-x

Pradier L, Tissot T, Fiston-Lavier AS, Bedhomme S. 2021. PlasForest: a homology-based random forest classifier for plasmid detection in genomic datasets. *BMC Bioinformatics* **22**:349. DOI: https://doi.org/10.1186/s12859-021-04270-w, PMID: 34174810

Ramirez MS, Tolmasky ME. 2010. Aminoglycoside modifying enzymes. *Drug Resistance Updates* **13**:151–171. DOI: https://doi.org/10.1016/j drup.2010.08.003, PMID: 20833577

Rather PN. 1998. Origins of the aminoglycoside modifying enzymes. *Drug Resistance Updates* **1**:285–291. DOI: https://doi.org/10.1016/s1368-7646(98)80044-7, PMID: 17092809

Ribeiro da Cunha B, Fonseca LP, Calado CRC. 2019. Antibiotic discovery: where have we come from, where do we go? *Antibiotics* **8**:45. DOI: https://doi.org/10.3390/antibiotics8020045, PMID: 31022923

Rousset F, Ferdy JB. 2014. Testing environmental and genetic effects in the presence of spatial autocorrelation. *Ecography* **37**:781–790. DOI: https://doi.org/10.1111/ecog.00566

Sabuncu E, David J, Bernède-Bauduin C, Pépin S, Leroy M, Boëlle PY, Watier L, Guillemot D. 2009. Significant reduction of antibiotic use in the community after a nationwide campaign in france, 2002-2007. *PLOS Medicine* **6**:e1000084. DOI: https://doi.org/10.1371/journal.pmed.1000084, PMID: 19492093

Salipante SJ, Hall BG. 2003. Determining the limits of the evolutionary potential of an antibiotic resistance gene. *Molecular Biology and Evolution* **20**:653–659. DOI: https://doi.org/10.1093/molbev/msg074, PMID: 12679553

Sandegren L, Andersson DI. 2009. Bacterial gene amplification: implications for the evolution of antibiotic resistance. *Nature Reviews. Microbiology* **7**:578–588. DOI: https://doi.org/10.1038/nrmicro2174, PMID: 19609259

Sander P, Meier A, Böttger EC. 1995. RpsL: a dominant selectable marker for gene replacement in mycobacteria. *Molecular Microbiology* **16**:991–1000. DOI: https://doi.org/10.1111/j.1365-2958.1995.tb02324.x, PMID: 7476195

San Millan A, MacLean RC. 2017. Fitness costs of plasmids: a limit to plasmid transmission. *Microbiology Spectrum* **5**:0016-2017. DOI: https://doi.org/10.1128/microbiolspec.MTBP-0016-2017, PMID: 28944751

Schrijver R, Stijntjes M, Rodríguez-Baño J, Tacconelli E, Babu Rajendran N, Voss A. 2018. Review of antimicrobial resistance surveillance programmes in livestock and meat in Eu with focus on humans. *Clinical Microbiology and Infection* **24**:577–590. DOI: https://doi.org/10.1016/j.cmi.2017.09.013, PMID: 28970159

Schroeder PJ, Jenkins DG. 2018. How robust are popular beta diversity indices to sampling error? *Ecosphere* **9**:e02100. DOI: https://doi.org/10.1002/ecs2.2100

Seemann T. 2014. Prokka: rapid prokaryotic genome annotation. *Bioinformatics* **30**:2068–2069. DOI: https://doi.org/10.1093/bioinformatics/btu153, PMID: 24642063

Seiler C, Berendonk TU. 2012. Heavy metal driven co-selection of antibiotic resistance in soil and water bodies impacted by agriculture and aquaculture. *Frontiers in Microbiology* **3**:399. DOI: https://doi.org/10.3389/fmicb.2012.00399, PMID: 23248620

Sievers F, Higgins DG. 2014. Clustal omega. *Current Protocols in Bioinformatics* **48**:3. DOI: https://doi.org/10.1002/0471250953.bi0313s48, PMID: 25501942

Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. 2006. ISfinder: the reference centre for bacterial insertion sequences. *Nucleic Acids Research* **34**:D32–D36. DOI: https://doi.org/10.1093/nar/gkj014, PMID: 16381877

South A. 2011. Rworldmap: a new R package for mapping global data. *The R Journal* **3**:35. DOI: https://doi.org/10.32614/RJ-2011-006
Murray BE, Murray B. 1991. New aspects of antimicrobial resistance and the resulting therapeutic dilemmas. *Journal of Infectious Diseases* **163**:1185–1194. DOI: https://doi.org/10.1093/infdis/163.6.1185

Nellums LB, Thompson H, Holmes A, Castro-Sánchez E, Otter JA, Norredam M, Friedland JS, Hargreaves S. 2018. Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis. *The Lancet*. *Infectious Diseases* **18**:796–811. DOI: https://doi.org/10.1016/S1473-3099(18)30219-6, PMID: 29779917

O'Neill J. 2014. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Review on Antimicrobial Resistance.

Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ. 2015. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. *BMC Genomics* **16**:964. DOI: https://doi.org/10.1186/s12864-015-2153-5, PMID: 26576951

Parks DH, Chuvochina M, Waite DW, Rinke C, Skarshewski A, Chaumeil PA, Hugenholtz P. 2018. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. *Nature Biotechnology* **36**:996–1004. DOI: https://doi.org/10.1038/nbt.4229, PMID: 30148503

Pehrsson EC, Tsukayama P, Patel S, Mejía-Bautista M, Sosa-Soto G, Navarrete KM, Calderon M, Cabrera L, Hoyos-Arango W, Bertoli MT, Berg DE, Gilman RH, Dantas G. 2016. Interconnected microbiomes and resistomes in low-income human habitats. *Nature* **533**:212–216. DOI: https://doi.org/10.1038/nature17672, PMID: 27172044

Perron GG, Whyte L, Turnbaugh PJ, Goordial J, Hanage WP, Dantas G, Desai MM. 2015. Functional characterization of bacteria isolated from ancient Arctic soil exposes diverse resistance mechanisms to modern antibiotics. *PLOS ONE* **10**:e0069533. DOI: https://doi.org/10.1371/journal.pone.0069533, PMID: 25807523

Pitta DW, Dou Z, Kumar S, Indugu N, Toth JD, Vecchiarelli B, Bhukya B. 2016. Metagenomic evidence of the prevalence and distribution patterns of antimicrobial resistance genes in dairy agroecosystems. *Foodborne Pathogens and Disease* **13**:296–302. DOI: https://doi.org/10.1089/fpd.2015.2092, PMID: 27046731

Podolsky SH. 2018. The evolving response to antibiotic resistance (1945–2018). *Palgrave Communications* **4**:1–8. DOI: https://doi.org/10.1057/s41599-018-0181-x

Pradier L, Tissot T, Fiston-Lavier AS, Bedhomme S. 2021. PlasForest: a homology-based random forest classifier for plasmid detection in genomic datasets. *BMC Bioinformatics* **22**:349. DOI: https://doi.org/10.1186/s12859-021-04270-w, PMID: 34174810

Ramirez MS, Tolmasky ME. 2010. Aminoglycoside modifying enzymes. *Drug Resistance Updates* **13**:151–171. DOI: https://doi.org/10.1016/j drup.2010.08.003, PMID: 20833577

Rather PN. 1998. Origins of the aminoglycoside modifying enzymes. *Drug Resistance Updates* **1**:285–291. DOI: https://doi.org/10.1016/s1368-7646(98)80044-7, PMID: 17092809

Ribeiro da Cunha B, Fonseca LP, Calado CRC. 2019. Antibiotic discovery: where have we come from, where do we go? *Antibiotics* **8**:45. DOI: https://doi.org/10.3390/antibiotics8020045, PMID: 31022923

Rousset F, Ferdy JB. 2014. Testing environmental and genetic effects in the presence of spatial autocorrelation. *Ecography* **37**:781–790. DOI: https://doi.org/10.1111/ecog.00566

Sabuncu E, David J, Bernède-Bauduin C, Pépin S, Leroy M, Boëlle PY, Watier L, Guillemot D. 2009. Significant reduction of antibiotic use in the community after a nationwide campaign in france, 2002-2007. *PLOS Medicine* **6**:e1000084. DOI: https://doi.org/10.1371/journal.pmed.1000084, PMID: 19492093

Salipante SJ, Hall BG. 2003. Determining the limits of the evolutionary potential of an antibiotic resistance gene. *Molecular Biology and Evolution* **20**:653–659. DOI: https://doi.org/10.1093/molbev/msg074, PMID: 12679553

Sandegren L, Andersson DI. 2009. Bacterial gene amplification: implications for the evolution of antibiotic resistance. *Nature Reviews. Microbiology* **7**:578–588. DOI: https://doi.org/10.1038/nrmicro2174, PMID: 19609259

Sander P, Meier A, Böttger EC. 1995. RpsL: a dominant selectable marker for gene replacement in mycobacteria. *Molecular Microbiology* **16**:991–1000. DOI: https://doi.org/10.1111/j.1365-2958.1995.tb02324.x, PMID: 7476195

San Millan A, MacLean RC. 2017. Fitness costs of plasmids: a limit to plasmid transmission. *Microbiology Spectrum* **5**:0016-2017. DOI: https://doi.org/10.1128/microbiolspec.MTBP-0016-2017, PMID: 28944751

Schrijver R, Stijntjes M, Rodríguez-Baño J, Tacconelli E, Babu Rajendran N, Voss A. 2018. Review of antimicrobial resistance surveillance programmes in livestock and meat in Eu with focus on humans. *Clinical Microbiology and Infection* **24**:577–590. DOI: https://doi.org/10.1016/j.cmi.2017.09.013, PMID: 28970159

Schroeder PJ, Jenkins DG. 2018. How robust are popular beta diversity indices to sampling error? *Ecosphere* **9**:e02100. DOI: https://doi.org/10.1002/ecs2.2100

Seemann T. 2014. Prokka: rapid prokaryotic genome annotation. *Bioinformatics* **30**:2068–2069. DOI: https://doi.org/10.1093/bioinformatics/btu153, PMID: 24642063

Seiler C, Berendonk TU. 2012. Heavy metal driven co-selection of antibiotic resistance in soil and water bodies impacted by agriculture and aquaculture. *Frontiers in Microbiology* **3**:399. DOI: https://doi.org/10.3389/fmicb.2012.00399, PMID: 23248620

Sievers F, Higgins DG. 2014. Clustal omega. *Current Protocols in Bioinformatics* **48**:3. DOI: https://doi.org/10.1002/0471250953.bi0313s48, PMID: 25501942

Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. 2006. ISfinder: the reference centre for bacterial insertion sequences. *Nucleic Acids Research* **34**:D32–D36. DOI: https://doi.org/10.1093/nar/gkj014, PMID: 16381877

South A. 2011. Rworldmap: a new R package for mapping global data. *The R Journal* **3**:35. DOI: https://doi.org/10.32614/RJ-2011-006
**Spicknall IH**, Foxman B, Marrs CF, Eisenberg JNS. 2013. A modeling framework for the evolution and spread of antibiotic resistance. *Literature Review and Model Categorization*. Am J Epidemiol **178**:508–520. DOI: https://doi.org/10.1093/aje/kwt017, PMID: 23660797

**Tello A**, Austin B, Telfer TC. 2012. Selective pressure of antibiotic pollution on bacteria of importance to public health. *Environmental Health Perspectives* **120**:1100–1106. DOI: https://doi.org/10.1289/ehp.1104650, PMID: 22571927

**Toivonen JM**, Boocock MR, Jacobs HT. 1999. Modelling in *Escherichia coli* of mutations in mitoribosomal protein S12: novel mutant phenotypes of rpsL. *Molecular Microbiology* **31**:1735–1746. DOI: https://doi.org/10.1046/j.1365-2958.1999.01307.x, PMID: 10209746

**Tripathi V**, Cytryn E. 2017. Impact of anthropogenic activities on the dissemination of antibiotic resistance across ecological boundaries. *Essays in Biochemistry* **61**:11–21. DOI: https://doi.org/10.1042/EBC20160054, PMID: 28258226

**Umweltbundesamt**. 2016. Pharmaceuticals in the Environment: Global Occurrence and Potential Cooperative Action under the Strategic Approach to International Chemicals Management (SAICM). Umweltbundesamt Texte.

**United Nations Conference for Trade and Development**. 2021. UNCTADstat. https://unctadstat.unctad.org/ [Accessed October 12, 2021].

**van Duijkeren E**, Schwarz C, Bouchard D, Catry B, Pomba C, Baptiste KE, Moreno MA, Rantala M, Ružauskas M, Sanders P, Teale C, Wester AL, Ignate K, Kunsagi Z, Jukes H. 2019. The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review. *The Journal of Antimicrobial Chemotherapy* **74**:2480–2496. DOI: https://doi.org/10.1093/jac/dkz161, PMID: 31002332

**van Hoek A**, Mevius D, Guerra B, Mullany P, Roberts AP, Aarts HJM. 2011. Acquired antibiotic resistance genes: an overview. *Frontiers in Microbiology* **2**:203. DOI: https://doi.org/10.3389/fmicb.2011.00203, PMID: 22046172

**Vaz-Moreira I**, Nunes OC, Manaia CM. 2014. Bacterial diversity and antibiotic resistance in water habitats: searching the links with the human microbiome. *FEMS Microbiology Reviews* **38**:761–778. DOI: https://doi.org/10.1111/1574-6976.12062, PMID: 24484530

**Watanabe T**. 1963. Infective heredity of multiple drug resistance in bacteria. *Bacteriological Reviews* **27**:87–115. DOI: https://doi.org/10.1128/br.27.1.87-115.1963, PMID: 13999115

**WHO Collaborating Centre for Drug Statistics Methodology**. 2020. WHOCC - ATC/DDD Index. https://www.whocc.no/atc_ddd_index/?code=J01GB06 [Accessed October 12, 2021].

**Witzany C**, Bonhoeffer S, Rolff J. 2020. Is antimicrobial resistance evolution accelerating? *PLOS Pathogens* **16:e1008905**. DOI: https://doi.org/10.1371/journal.ppat.1008905, PMID: 33091083

**World Bank**. 2021a. World Bank Open Data. https://data.worldbank.org/ [Accessed October 14, 2021].

**World Bank**. 2021b. Global Bilateral Migration Database. https://databank.worldbank.org/source/global-bilateral-migration [Accessed October 14, 2021].

**World Health Organization**. 2015. Global Action Plan on Antimicrobial Resistance. WHO.

**Zárate SG**, De la Cruz Claure ML, Benito-Arenas R, Revuelta J, Santana AG, Bastida A. 2018. Overcoming aminoglycoside enzymatic resistance: design of novel antibiotics and inhibitors. *Molecules* **23**:284. DOI: https://doi.org/10.3390/molecules23020284, PMID: 29385736

**Zhai Y**, He Z, Kang Y, Yu H, Wang J, Du P, Zhang Z, Hu S, Gao Z. 2016. Complete nucleotide sequence of ph11, an inchi2 plasmid conferring multi-antibiotic resistance and multi-heavy metal resistance genes in a clinical klebsiella pneumoniae isolate. *Plasmid* **86**:26–31. DOI: https://doi.org/10.1016/j.plasmid.2016.04.001, PMID: 27101788

**Zhang AN**, Hou CJ, Negi M, Li LG, Zhang T. 2020. Online searching platform for the antibiotic resistome in bacterial tree of life and global habitats. *FEMS Microbiology Ecology* **96**:107. DOI: https://doi.org/10.1093/femsec/fiaa107, PMID: 32472933

**Zurfluh K**, Nüesch-Inderbinen M, Morach M, Zihler Berner A, Hächler H, Stephan R. 2015. Extended-Spectrum-B-Lactamase-Producing Enterobacteriaceae isolated from vegetables imported from the Dominican Republic, India, Thailand, and Vietnam. *Applied and Environmental Microbiology* **81**:3115–3120. DOI: https://doi.org/10.1128/AEM.00258-15, PMID: 25724954
**Spicknall IH**, Foxman B, Marrs CF, Eisenberg JNS. 2013. A modeling framework for the evolution and spread of antibiotic resistance. *Literature Review and Model Categorization*. Am J Epidemiol **178**:508–520. DOI: https://doi.org/10.1093/aje/kwt017, PMID: 23660797

**Tello A**, Austin B, Telfer TC. 2012. Selective pressure of antibiotic pollution on bacteria of importance to public health. *Environmental Health Perspectives* **120**:1100–1106. DOI: https://doi.org/10.1289/ehp.1104650, PMID: 22571927

**Toivonen JM**, Boocock MR, Jacobs HT. 1999. Modelling in *Escherichia coli* of mutations in mitoribosomal protein S12: novel mutant phenotypes of rpsL. *Molecular Microbiology* **31**:1735–1746. DOI: https://doi.org/10.1046/j.1365-2958.1999.01307.x, PMID: 10209746

**Tripathi V**, Cytryn E. 2017. Impact of anthropogenic activities on the dissemination of antibiotic resistance across ecological boundaries. *Essays in Biochemistry* **61**:11–21. DOI: https://doi.org/10.1042/EBC20160054, PMID: 28258226

**Umweltbundesamt**. 2016. Pharmaceuticals in the Environment: Global Occurrence and Potential Cooperative Action under the Strategic Approach to International Chemicals Management (SAICM). Umweltbundesamt Texte.

**United Nations Conference for Trade and Development**. 2021. UNCTADstat. https://unctadstat.unctad.org/ [Accessed October 12, 2021].

**van Duijkeren E**, Schwarz C, Bouchard D, Catry B, Pomba C, Baptiste KE, Moreno MA, Rantala M, Ružauskas M, Sanders P, Teale C, Wester AL, Ignate K, Kunsagi Z, Jukes H. 2019. The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review. *The Journal of Antimicrobial Chemotherapy* **74**:2480–2496. DOI: https://doi.org/10.1093/jac/dkz161, PMID: 31002332

**van Hoek A**, Mevius D, Guerra B, Mullany P, Roberts AP, Aarts HJM. 2011. Acquired antibiotic resistance genes: an overview. *Frontiers in Microbiology* **2**:203. DOI: https://doi.org/10.3389/fmicb.2011.00203, PMID: 22046172

**Vaz-Moreira I**, Nunes OC, Manaia CM. 2014. Bacterial diversity and antibiotic resistance in water habitats: searching the links with the human microbiome. *FEMS Microbiology Reviews* **38**:761–778. DOI: https://doi.org/10.1111/1574-6976.12062, PMID: 24484530

**Watanabe T**. 1963. Infective heredity of multiple drug resistance in bacteria. *Bacteriological Reviews* **27**:87–115. DOI: https://doi.org/10.1128/br.27.1.87-115.1963, PMID: 13999115

**WHO Collaborating Centre for Drug Statistics Methodology**. 2020. WHOCC - ATC/DDD Index. https://www.whocc.no/atc_ddd_index/?code=J01GB06 [Accessed October 12, 2021].

**Witzany C**, Bonhoeffer S, Rolff J. 2020. Is antimicrobial resistance evolution accelerating? *PLOS Pathogens* **16:e1008905**. DOI: https://doi.org/10.1371/journal.ppat.1008905, PMID: 33091083

**World Bank**. 2021a. World Bank Open Data. https://data.worldbank.org/ [Accessed October 14, 2021].

**World Bank**. 2021b. Global Bilateral Migration Database. https://databank.worldbank.org/source/global-bilateral-migration [Accessed October 14, 2021].

**World Health Organization**. 2015. Global Action Plan on Antimicrobial Resistance. WHO.

**Zárate SG**, De la Cruz Claure ML, Benito-Arenas R, Revuelta J, Santana AG, Bastida A. 2018. Overcoming aminoglycoside enzymatic resistance: design of novel antibiotics and inhibitors. *Molecules* **23**:284. DOI: https://doi.org/10.3390/molecules23020284, PMID: 29385736

**Zhai Y**, He Z, Kang Y, Yu H, Wang J, Du P, Zhang Z, Hu S, Gao Z. 2016. Complete nucleotide sequence of ph11, an inchi2 plasmid conferring multi-antibiotic resistance and multi-heavy metal resistance genes in a clinical klebsiella pneumoniae isolate. *Plasmid* **86**:26–31. DOI: https://doi.org/10.1016/j.plasmid.2016.04.001, PMID: 27101788

**Zhang AN**, Hou CJ, Negi M, Li LG, Zhang T. 2020. Online searching platform for the antibiotic resistome in bacterial tree of life and global habitats. *FEMS Microbiology Ecology* **96**:107. DOI: https://doi.org/10.1093/femsec/fiaa107, PMID: 32472933

**Zurfluh K**, Nüesch-Inderbinen M, Morach M, Zihler Berner A, Hächler H, Stephan R. 2015. Extended-Spectrum-B-Lactamase-Producing Enterobacteriaceae isolated from vegetables imported from the Dominican Republic, India, Thailand, and Vietnam. *Applied and Environmental Microbiology* **81**:3115–3120. DOI: https://doi.org/10.1128/AEM.00258-15, PMID: 25724954