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Defining and combating antibiotic resistance from One Health and Global Health perspectives


Several interconnected human, animal and environmental habitats can contribute to the emergence, evolution and spread of antibiotic resistance, and the health of these contiguous habitats (the focus of the One Health approach) may represent a risk to human health. Additionally, the expansion of resistant clones and antibiotic resistance determinants among human-associated, animal-associated and environmental microbiomes have the potential to alter bacterial population genetics at local and global levels, thereby modifying the structure, and eventually the productivity, of microbiomes where antibiotic-resistant bacteria can expand. Conversely, any change in these habitats (including pollution by antibiotics or by antibiotic-resistant organisms) may influence the structures of their associated bacterial populations, which might affect the spread of antibiotic resistance to, and among, the above-mentioned microbiomes. Besides local transmission among connected habitats—the focus of studies under the One Health concept—the transmission of resistant microorganisms might occur on a broader (even worldwide) scale, requiring coordinated Global Health actions. This Review provides updated information on the elements involved in the evolution and spread of antibiotic resistance at local and global levels, and proposes studies to be performed and strategies to be followed that may help reduce the burden of antibiotic resistance as well as its impact on human and planetary health.

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Fig. 1: The One Health and global Health axes of antibiotic resistance.
Fig. 2: The hierarchy and spread of antibiotic resistance.


  1. 1.

    Berendonk, T. U. et al. Tackling antibiotic resistance: the environmental framework. Nat. Rev. Microbiol. 13, 310–317 (2015).

    CAS  PubMed  Google Scholar 

  2. 2.

    Koplan, J. P. et al. Towards a common definition of global health. Lancet 373, 1993–1995 (2009).

    PubMed  Google Scholar 

  3. 3.

    Wernli, D. et al. Mapping global policy discourse on antimicrobial resistance. BMJ Glob. Health 2, e000378 (2017).

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Global Action Plan on Antimicrobial Resistance (WHO, 2015).

  5. 5.

    Tackling antimicrobial resistance 2019 to 2024: the UK’s 5-year national action plan (UK Government, 2019).

  6. 6.

    Collignon, P., Beggs, J. J., Walsh, T. R., Gandra, S. & Laxminarayan, R. Anthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysis. Lancet Planet. Health 2, e398–e405 (2018).

    PubMed  Google Scholar 

  7. 7.

    Antibiotic Resistance. WHO (2018).

  8. 8.

    Donker, T., Wallinga, J., Slack, R. & Grundmann, H. Hospital networks and the dispersal of hospital-acquired pathogens by patient transfer. PloS ONE 7, e35002 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Tacconelli, E. et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 18, 318–327 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Lanza, V. F. et al. In-depth resistome analysis by targeted metagenomics. Microbiome 6, 11 (2018).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Pärnänen, K. M. M. et al. Antibiotic resistance in European wastewater treatment plants mirrors the pattern of clinical antibiotic resistance prevalence. Sci. Adv. 5, eaau9124 (2019).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Martinez, J. L. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. Front. Microbiol. 3, 265 (2012).

    Google Scholar 

  13. 13.

    Campos, M. et al. Simulating multilevel dynamics of antimicrobial resistance in a membrane computing model. mBio 10, e02460–18 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Chatterjee, A. et al. Quantifying drivers of antibiotic resistance in humans: a systematic review. Lancet Infect. Dis. 18, e368–e378 (2018).

    CAS  PubMed  Google Scholar 

  15. 15.

    Martinez, J. L. & Baquero, F. Emergence and spread of antibiotic resistance: setting a parameter space. Upsala J. Med. Sci. 119, 68–77 (2014).

    PubMed  Google Scholar 

  16. 16.

    Pehrsson, E. C. et al. Interconnected microbiomes and resistomes in low-income human habitats. Nature 533, 212–216 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Potron, A., Poirel, L. & Nordmann, P. Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in Shewanella xiamenensis. Antimicrob. Agents Ch. 55, 4405–4407 (2011).

    CAS  Google Scholar 

  18. 18.

    Poirel, L., Rodriguez-Martinez, J. M., Mammeri, H., Liard, A. & Nordmann, P. Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob. Agents Ch. 49, 3523–3525 (2005).

    CAS  Google Scholar 

  19. 19.

    Caudell, M. A. et al. Identification of risk factors associated with carriage of resistant Escherichia coli in three culturally diverse ethnic groups in Tanzania: a biological and socioeconomic analysis. Lancet Planet. Health 2, e489–e497 (2018).

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Baquero, F. Transmission as a basic process in microbial biology. Lwoff Award Prize Lecture. FEMS Microbiol. Rev. 41, 816–827 (2017).

    CAS  PubMed  Google Scholar 

  21. 21.

    Price, L. B., Hungate, B. A., Koch, B. J., Davis, G. S. & Liu, C. M. Colonizing opportunistic pathogens (COPs): the beasts in all of us. PLoS Pathog. 13, e1006369 (2017).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Sheppard, S. K., Guttman, D. S. & Fitzgerald, J. R. Population genomics of bacterial host adaptation. Nat. Rev. Genet. 19, 549–565 (2018).

    CAS  PubMed  Google Scholar 

  23. 23.

    Muloi, D. et al. Are food animals responsible for transfer of antimicrobial-resistant Escherichia coli or their resistance determinants to human populations? A systematic review. Foodborne Pathog. Dis. 15, 467–474 (2018).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Wu, S. et al. Staphylococcus aureus isolated from retail meat and meat products in China: incidence, antibiotic resistance and genetic diversity. Front. Microbiol. 9, 2767 (2018).

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Liu, C. M. et al. Escherichia coli ST131-H22 as a foodborne uropathogen. mBio 9, e00470–18 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Spoor, L. E. et al. Livestock origin for a human pandemic clone of community-associated methicillin-resistant Staphylococcus aureus. mBio 4, e00356–13 (2013).

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Price, L. B. et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. mBio 3, e00305–11 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Uhlemann, A. C. et al. Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties. mBio 3, e00027–12 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Leekitcharoenphon, P. et al. Global genomic epidemiology of Salmonella enterica serovar Typhimurium DT104. Appl. Environ. Microb. 82, 2516–2526 (2016).

    CAS  Google Scholar 

  30. 30.

    Mather, A. E. et al. Distinguishable epidemics of multidrug-resistant Salmonella Typhimurium DT104 in different hosts. Science 341, 1514–1517 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Hu, Y. et al. The bacterial mobile resistome transfer network connecting the animal and human microbiomes. Appl. Environ. Microb. 82, 6672–6681 (2016).

    CAS  Google Scholar 

  32. 32.

    de Been, M. et al. Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages. PLoS Genet. 10, e1004776 (2014).

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Matamoros, S. et al. Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction. Sci. Rep. 7, 15364 (2017).

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Klemm, E. J. et al. Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio 9, e00105–18 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Freitas, A. R. et al. Multilevel population genetic analysis of vanA and vanB Enterococcus faecium causing nosocomial outbreaks in 27 countries (1986–2012). J. Antimicrob. Chemoth. 71, 3351–3366 (2016).

    CAS  Google Scholar 

  36. 36.

    Kumarasamy, K. K. et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect. Dis. 10, 597–602 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Fitzpatrick, D. & Walsh, F. Antibiotic resistance genes across a wide variety of metagenomes. FEMS Microbiol. Ecol. 92, fiv168 (2016).

    PubMed  Google Scholar 

  38. 38.

    Loncaric, I. et al. Comparison of ESBL–and AmpC producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA) isolated from migratory and resident population of rooks (Corvus frugilegus) in Austria. PloS ONE 8, e84048 (2013).

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Segawa, T. et al. Distribution of antibiotic resistance genes in glacier environments. Environ. Microbiol. Rep. 5, 127–134 (2013).

    CAS  PubMed  Google Scholar 

  40. 40.

    McDougall, F., Boardman, W., Gillings, M. & Power, M. Bats as reservoirs of antibiotic resistance determinants: A survey of class 1 integrons in grey-headed flying foxes (Pteropus poliocephalus). Infect. Genet. Evol. 70, 107–113 (2019).

    CAS  PubMed  Google Scholar 

  41. 41.

    Clemente, J. et al. The microbiome of uncontacted Amerindians. Sci. Adv. 1, e1500183 (2015).

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Knapp, C. W., Dolfing, J., Ehlert, P. A. & Graham, D. W. Evidence of increasing antibiotic resistance gene abundances in archived soils since 1940. Environ. Sci. Technol. 44, 580–587 (2010).

    CAS  PubMed  Google Scholar 

  43. 43.

    Enright, M. C. et al. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc. Natl Acad. Sci. USA 99, 7687–7692 (2002).

    CAS  PubMed  Google Scholar 

  44. 44.

    Chen, M. Y. et al. Multilevel selection of bcrABDR-mediated bacitracin resistance in Enterococcus faecalis from chicken farms. Sci. Rep. 6, 34895 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Fondi, M. et al. “Every gene is everywhere but the environment selects”: global geolocalization of gene sharing in environmental samples through network analysis. Genome Biol. Evol. 8, 1388–1400 (2016).

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Ingle, D. J., Levine, M. M., Kotloff, K. L., Holt, K. E. & Robins-Browne, R. M. Dynamics of antimicrobial resistance in intestinal Escherichia coli from children in community settings in South Asia and sub-Saharan Africa. Nat. Microbiol. 3, 1063–1073 (2018).

    CAS  PubMed  Google Scholar 

  47. 47.

    Martinez, J. L., Coque, T. M. & Baquero, F. What is a resistance gene? Ranking risk in resistomes. Nat. Rev. Microbiol. 13, 116–123 (2015).

    CAS  PubMed  Google Scholar 

  48. 48.

    Forsberg, K. J. et al. The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107–1111 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Sommer, M. O., Dantas, G. & Church, G. M. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325, 1128–1131 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Ruppé, E. et al. Prediction of the intestinal resistome by a three-dimensional structure-based method. Nat. Microbiol. 4, 112–123 (2019).

    PubMed  Google Scholar 

  51. 51.

    Gray, G. C. & Merchant, J. A. Pigs, pathogens, and public health. Lancet Infect. Dis. 18, 372–373 (2018).

    PubMed  Google Scholar 

  52. 52.

    Ramankutty, N. et al. Trends in global agricultural land use: implications for environmental health and food security. Annu. Rev. Plant Biol. 69, 789–815 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Okeke, I. N. & Edelman, R. Dissemination of antibiotic-resistant bacteria across geographic borders. Clin. Infect. Dis. 33, 364–369 (2001).

    CAS  PubMed  Google Scholar 

  54. 54.

    Sieber, R. N. et al. Drivers and dynamics of methicillin-resistant livestock-associated Staphylococcus aureus CC398 in pigs and humans in Denmark. mBio 9, e02142–18 (2018).

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Reuland, E. A. et al. Travel to Asia and traveller’s diarrhoea with antibiotic treatment are independent risk factors for acquiring ciprofloxacin-resistant and extended spectrum beta-lactamase-producing Enterobacteriaceae-a prospective cohort study. Clin. Microbiol. Infect. 22, 731.e1–731.e7 (2016).

    CAS  Google Scholar 

  56. 56.

    Murray, B. E., Mathewson, J. J., DuPont, H. L., Ericsson, C. D. & Reves, R. R. Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents. Antimicrob. Agents Ch. 34, 515–518 (1990).

    CAS  Google Scholar 

  57. 57.

    Angeletti, S. et al. Unusual microorganisms and antimicrobial resistances in a group of Syrian migrants: Sentinel surveillance data from an asylum seekers centre in Italy. Travel Med. Infect. Dis. 14, 115–122 (2016).

    PubMed  Google Scholar 

  58. 58.

    Ciccozzi, M. et al. Sentinel surveillance data from Eritrean migrants in Italy: The theory of “Healthy Migrants”. Travel Med. Infect. Dis. 22, 58–65 (2018).

    PubMed  Google Scholar 

  59. 59.

    Aldridge, R. W. et al. Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland. Lancet 388, 2510–2518 (2016).

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Yasin, Y., Biehl, K. & Erol, M. Infection of the Invisible: impressions of a tuberculosis intervention program for migrants in Istanbul. J. Immigr. Minor. Heal. 17, 1481–1486 (2015).

    Google Scholar 

  61. 61.

    Klein, E. Y. et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc. Natl Acad. Sci. USA 115, E3463–E3470 (2018).

    CAS  PubMed  Google Scholar 

  62. 62.

    Auta, A. et al. Global access to antibiotics without prescription in community pharmacies: a systematic review and meta-analysis. J. Infect. 78, 8–18 (2019).

    PubMed  Google Scholar 

  63. 63.

    Yong Kim, J. et al. Limited good and limited vision: multidrug-resistant tuberculosis and global health policy. Soc. Sci. Med. 61, 847–859 (2005).

    PubMed  Google Scholar 

  64. 64.

    Keenan, J. D. et al. Azithromycin to reduce childhood mortality in Sub-Saharan. Afr. New Engl. J. Med. 378, 1583–1592 (2018).

    CAS  Google Scholar 

  65. 65.

    Done, H. Y., Venkatesan, A. K. & Halden, R. U. Does the recent growth of aquaculture create antibiotic resistance threats different from those associated with land animal production in agriculture? AAPS J. 17, 513–524 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Aarestrup, F. M. et al. Effect of abolishment of the use of antimicrobial agents for growth promotion on occurrence of antimicrobial resistance in fecal enterococci from food animals in Denmark. Antimicrob. Agents Ch. 45, 2054–2059 (2001).

    CAS  Google Scholar 

  67. 67.

    Van Boeckel, T. P. et al. Reducing antimicrobial use in food animals. Science 357, 1350–1352 (2017).

    PubMed  Google Scholar 

  68. 68.

    Van Boeckel, T. P. et al. Global trends in antimicrobial use in food animals. Proc. Natl Acad. Sci. USA 112, 5649–5654 (2015).

    Google Scholar 

  69. 69.

    Dowling, R. et al. Estimating the prevalence of toxic waste sites in low- and middle-income countries. Ann. Glob. Health 82, 700–710 (2016).

    PubMed  Google Scholar 

  70. 70.

    Fang, L. et al. Co-spread of metal and antibiotic resistance within ST3-IncHI2 plasmids from E. coli isolates of food-producing animals. Sci. Rep. 6, 25312 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Jutkina, J., Marathe, N. P., Flach, C. F. & Larsson, D. G. J. Antibiotics and common antibacterial biocides stimulate horizontal transfer of resistance at low concentrations. Sci. Total Environ. 616–617, 172–178 (2018).

    PubMed  Google Scholar 

  72. 72.

    Hsu, L. C. et al. Adsorption of tetracycline on Fe (hydr)oxides: effects of pH and metal cation (Cu(2. Zn.(2+) Al(3+)) addition in various molar ratios. Roy. Soc. Open Sci. 5, 171941 (2018).

    Google Scholar 

  73. 73.

    Karkman, A., Parnanen, K. & Larsson, D. G. J. Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments. Nat. Commun. 10, 80 (2019).

    PubMed  PubMed Central  Google Scholar 

  74. 74.

    Walsh, T. R., Weeks, J., Livermore, D. M. & Toleman, M. A. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect. Dis. 11, 355–362 (2011).

    PubMed  Google Scholar 

  75. 75.

    Ma, L. et al. Catalogue of antibiotic resistome and host-tracking in drinking water deciphered by a large scale survey. Microbiome 5, 154 (2017).

    PubMed  PubMed Central  Google Scholar 

  76. 76.

    Leonard, A. F. C. et al. Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: Environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey). Environ. Int. 114, 326–333 (2018).

    PubMed  Google Scholar 

  77. 77.

    Hendriksen, R. S. et al. Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage. Nat. Commun. 10, 1124 (2019).

    PubMed  PubMed Central  Google Scholar 

  78. 78.

    Moura, A., Henriques, I., Smalla, K. & Correia, A. Wastewater bacterial communities bring together broad-host range plasmids, integrons and a wide diversity of uncharacterized gene cassettes. Res. Microbiol. 161, 58–66 (2010).

    CAS  PubMed  Google Scholar 

  79. 79.

    Yang, Y., Xu, C., Cao, X., Lin, H. & Wang, J. Antibiotic resistance genes in surface water of eutrophic urban lakes are related to heavy metals, antibiotics, lake morphology and anthropic impact. Ecotoxicology 26, 831–840 (2017).

    CAS  PubMed  Google Scholar 

  80. 80.

    Chin, W. et al. A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset. Nat. Commun. 9, 917 (2018).

    PubMed  PubMed Central  Google Scholar 

  81. 81.

    Rodriguez-Chueca, J. et al. Assessment of full-scale tertiary wastewater treatment by UV-C based-AOPs: Removal or persistence of antibiotics and antibiotic resistance genes? Sci. Total Environ. 652, 1051–1061 (2019).

    PubMed  Google Scholar 

  82. 82.

    Jojoa-Sierra, S. D., Silva-Agredo, J., Herrera-Calderon, E. & Torres-Palma, R. A. Elimination of the antibiotic norfloxacin in municipal wastewater, urine and seawater by electrochemical oxidation on IrO2 anodes. Sci. Total Environ. 575, 1228–1238 (2017).

    CAS  PubMed  Google Scholar 

  83. 83.

    Paulus, G. K. et al. The impact of on-site hospital wastewater treatment on the downstream communal wastewater system in terms of antibiotics and antibiotic resistance genes. Int. J. Hyg. Envir. Heal. 222, 635–644 (2019).

    CAS  Google Scholar 

  84. 84.

    Narciso-da-Rocha, C. et al. Bacterial lineages putatively associated with the dissemination of antibiotic resistance genes in a full-scale urban wastewater treatment plant. Environ. Int. 118, 179–188 (2018).

    CAS  PubMed  Google Scholar 

  85. 85.

    Su, H. C. et al. Antibiotic resistance, plasmid-mediated quinolone resistance (PMQR) genes and ampC gene in two typical municipal wastewater treatment plants. Environ. Sci.: Process. Impacts 16, 324–332 (2014).

    CAS  Google Scholar 

  86. 86.

    Hultman, J. et al. Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent. FEMS Microbiol. Ecol. 94, fiy038 (2018).

    PubMed Central  Google Scholar 

  87. 87.

    Fuller, T. et al. The ecology of emerging infectious diseases in migratory birds: an assessment of the role of climate change and priorities for future research. EcoHealth 9, 80–88 (2012).

    PubMed  Google Scholar 

  88. 88.

    Beugnet, F. & Chalvet-Monfray, K. Impact of climate change in the epidemiology of vector-borne diseases in domestic carnivores. Comp. Immunol. Micro. 36, 559–566 (2013).

    CAS  Google Scholar 

  89. 89.

    Martinez-Urtaza, J., Trinanes, J., Gonzalez-Escalona, N. & Baker-Austin, C. Is El Nino a long-distance corridor for waterborne disease? Nat. Microbiol. 1, 16018 (2016).

    CAS  PubMed  Google Scholar 

  90. 90.

    Yu, P. et al. Elevated levels of pathogenic indicator bacteria and antibiotic resistance genes after Hurricane Harvey’s flooding in Houston. Environ. Sci. Tech. Let. 5, 481–486 (2018).

    CAS  Google Scholar 

  91. 91.

    Bartlett, J. G., Gilbert, D. N. & Spellberg, B. Seven ways to preserve the miracle of antibiotics. Clin. Infect. Dis. 56, 1445–1450 (2013).

    CAS  PubMed  Google Scholar 

  92. 92.

    Brochado, A. R. et al. Species-specific activity of antibacterial drug combinations. Nature 559, 259–263 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Garcia-Fernandez, E. et al. Membrane microdomain disassembly inhibits MRSA antibiotic resistance. Cell 171, 1354–1367 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Jayaraman, P. et al. Novel phytochemical-antibiotic conjugates as multitarget inhibitors of Pseudomononas aeruginosa GyrB/ParE and DHFR. Drug Des. Dev. Ther. 7, 449–475 (2013).

    CAS  Google Scholar 

  95. 95.

    Li, K. et al. Multitarget drug discovery for tuberculosis and other infectious diseases. J. Med. Chem. 57, 3126–3139 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Theuretzbacher, U., Ardal, C. & Harbarth, S. Linking sustainable use policies to novel economic incentives to stimulate antibiotic research and development. Infect. Dis. Rep. 9, 6836 (2017).

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Rolain, J. M. & Baquero, F. The refusal of the Society to accept antibiotic toxicity: missing opportunities for therapy of severe infections. Clin. Microb. Infect. 22, 423–427 (2016).

    CAS  Google Scholar 

  98. 98.

    Oviano, M., Ramirez, C. L., Barbeyto, L. P. & Bou, G. Rapid direct detection of carbapenemase-producing Enterobacteriaceae in clinical urine samples by MALDI-TOF MS. Anal. J. Antimicrob. Chemoth 72, 1350–1354 (2017).

    CAS  Google Scholar 

  99. 99.

    Otero, F. et al. Rapid detection of antibiotic resistance in Gram-negative bacteria through assessment of changes in cellular morphology. Microb. Drug Resist. 23, 157–162 (2017).

    CAS  PubMed  Google Scholar 

  100. 100.

    Levin, B. R., Baquero, F. & Johnsen, P. J. A model-guided analysis and perspective on the evolution and epidemiology of antibiotic resistance and its future. Curr. Opin. Microbiol. 19, 83–89 (2014).

    PubMed  PubMed Central  Google Scholar 

  101. 101.

    Antonanzas, F. & Goossens, H. The economics of antibiotic resistance: a claim for personalised treatments. Eur. J. Health Econ. 20, 483–485 (2018).

    Google Scholar 

  102. 102.

    Pennini, M. E. et al. Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae. Nat. Commun. 8, 1991 (2017).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Silva, O. N. et al. An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities. Sci. Rep. 6, 35465 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Matthay, M. A. et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Resp. Med. 7, 154–162 (2019).

    Google Scholar 

  105. 105.

    Ni, Z., Chen, Y., Ong, E. & He, Y. Antibiotic resistance determinant-focused Acinetobacter baumannii vaccine designed using reverse vaccinology. Int. J. Mol. Sci. 18, E458 (2017).

    PubMed  Google Scholar 

  106. 106.

    Cabral, M. P. et al. Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy. Nat. Commun. 8, 15480 (2017).

    CAS  PubMed  Google Scholar 

  107. 107.

    Jansen, K. U. & Anderson, A. S. The role of vaccines in fighting antimicrobial resistance (AMR). Hum. Vacc. Immunother. 14, 2142–2149 (2018).

    Google Scholar 

  108. 108.

    Marchisio, P. et al. Efficacy of injectable trivalent virosomal-adjuvanted inactivated influenza vaccine in preventing acute otitis media in children with recurrent complicated or noncomplicated acute otitis media. Pediatr. Infect. Dis. J. 28, 855–859 (2009).

    PubMed  Google Scholar 

  109. 109.

    Campbell, Z. A., Otieno, L., Shirima, G. M., Marsh, T. L. & Palmer, G. H. Drivers of vaccination preferences to protect a low-value livestock resource: Willingness to pay for Newcastle disease vaccines by smallholder households. Vaccine 37, 11–18 (2019).

    PubMed  PubMed Central  Google Scholar 

  110. 110.

    Bessell, P. R. et al. Assessing the impact of a novel strategy for delivering animal health interventions to smallholder farmers. Prev. Vet. Med. 147, 108–116 (2017).

    PubMed  Google Scholar 

  111. 111.

    Shatzkes, K. et al. Predatory bacteria attenuate Klebsiella pneumoniae burden in rat lungs. mBio 7, e01847–16 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    de Dios Caballero, J. et al. Individual patterns of complexity in cystic fibrosis lung microbiota, including predator bacteria, over a 1-year period. mBio 8, e00959–17 (2017).

    PubMed  PubMed Central  Google Scholar 

  113. 113.

    Kongrueng, J. et al. Isolation of Bdellovibrio and like organisms and potential to reduce acute hepatopancreatic necrosis disease caused by Vibrio parahaemolyticus. Dis. Aquat. Organ. 124, 223–232 (2017).

    PubMed  Google Scholar 

  114. 114.

    Boileau, M. J. et al. Efficacy of Bdellovibrio bacteriovorus 109J for the treatment of dairy calves with experimentally induced infectious bovine keratoconjunctivitis. Am. J. Vet. Res. 77, 1017–1028 (2016).

    CAS  PubMed  Google Scholar 

  115. 115.

    McNeely, D., Chanyi, R. M., Dooley, J. S., Moore, J. E. & Koval, S. F. Biocontrol of Burkholderia cepacia complex bacteria and bacterial phytopathogens by Bdellovibrio bacteriovorus. Can. J. Microbiol. 63, 350–358 (2017).

    CAS  PubMed  Google Scholar 

  116. 116.

    Obolski, U., Stein, G. Y. & Hadany, L. Antibiotic restriction might facilitate the emergence of multi-drug resistance. PLoS Comput. Biol. 11, e1004340 (2015).

    PubMed  PubMed Central  Google Scholar 

  117. 117.

    Lehar, S. M. et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323–328 (2015).

    CAS  PubMed  Google Scholar 

  118. 118.

    de Gunzburg, J. et al. Protection of the human gut microbiome from antibiotics. J. Infect. Dis. 217, 628–636 (2018).

    PubMed  Google Scholar 

  119. 119.

    Chahm, T., de Souza, L. F., Dos Santos, N. R., da Silva, B. A. & Rodrigues, C. A. Use of chemically activated termite feces a low-cost adsorbent for the adsorption of norfloxacin from aqueous solution. Water Sci. Technol. Res. 79, 291–301 (2019).

    CAS  Google Scholar 

  120. 120.

    Chen, L. et al. Degradation of antibiotics in multi-component systems with novel ternary AgBr/Ag3PO4@natural hematite heterojunction photocatalyst under simulated solar light. J. hazard. Mater. 371, 566–575 (2019).

    CAS  PubMed  Google Scholar 

  121. 121.

    Kokai-Kun, J. F. et al. The oral beta-lactamase SYN-004 (ribaxamase) degrades ceftriaxone excreted into the intestine in phase 2a clinical studies. Antimicrob. Agents Ch. 61, e02197–16 (2017).

    CAS  Google Scholar 

  122. 122.

    Connelly, S., Fanelli, B., Hasan, N. A., Colwell, R. R. & Kaleko, M. Oral metallo-beta-lactamase protects the gut microbiome from carbapenem-mediated damage and reduces propagation of antibiotic resistance in pigs. Front. Microbiol. 10, 101 (2019).

    PubMed  PubMed Central  Google Scholar 

  123. 123.

    Ives, S. E. & Richeson, J. T. Use of antimicrobial metaphylaxis for the control of bovine respiratory disease in high-risk cattle. V. Clin. N. Am. -Food A 31, 341–350 (2015).

    Google Scholar 

  124. 124.

    Regev-Shoshani, G. et al. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot. Prev. Vet. Med. 138, 162–169 (2017).

    CAS  PubMed  Google Scholar 

  125. 125.

    Kudo, H. et al. Inhibition effect of flavophospholipol on conjugative transfer of the extended-spectrum beta-lactamase and vanA genes. J. Antibiot. 72, 79–85 (2019).

    CAS  PubMed  Google Scholar 

  126. 126.

    Lin, W., Li, S., Zhang, S. & Yu, X. Reduction in horizontal transfer of conjugative plasmid by UV irradiation and low-level chlorination. Water Res. 91, 331–338 (2016).

    CAS  PubMed  Google Scholar 

  127. 127.

    Suhartono, S. & Savin, M. Conjugative transmission of antibiotic-resistance from stream water Escherichia coli as related to number of sulfamethoxazole but not class 1 and 2 integrase genes. Mob. Genet. Elem. 6, e1256851 (2016).

    Google Scholar 

  128. 128.

    Cairns, J. et al. Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes. Commun. Biol. 1, 35 (2018).

    PubMed  PubMed Central  Google Scholar 

  129. 129.

    Brown, V. R. & Bevins, S. N. A review of African swine fever and the potential for introduction into the United States and the possibility of subsequent establishment in feral swine and native ticks. Front. Vet. Sci. 5, 11 (2018).

    PubMed  PubMed Central  Google Scholar 

  130. 130.

    Water, Sanitation & Hygiene: Reinvent the Toilet Challenge. Bill and Melinda Gates Foundation (2013).

  131. 131.

    Baquero, F., Coque, T. M. & de la Cruz, F. Ecology and evolution as targets: the need for novel eco-evo drugs and strategies to fight antibiotic resistance. Antimicrob. Agents Ch. 55, 3649–3660 (2011).

    CAS  Google Scholar 

  132. 132.

    Li, Q. et al. NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against beta-lactamase-producing strains. Antimicrob. Agents Ch. 46, 1262–1268 (2002).

    CAS  Google Scholar 

  133. 133.

    Jebastin, T. & Narayanan, S. In silico epitope identification of unique multidrug resistance proteins from Salmonella typhi for vaccine development. Comput. Biol. Chem. 78, 74–80 (2018).

    PubMed  Google Scholar 

  134. 134.

    Withey, S., Cartmell, E., Avery, L. M. & Stephenson, T. Bacteriophages–potential for application in wastewater treatment processes. Sci. Total Environ. 339, 1–18 (2005).

    CAS  PubMed  Google Scholar 

  135. 135.

    Vestergaard, M. et al. Inhibition of the ATP synthase eliminates the intrinsic resistance of Staphylococcus aureus towards polymyxins. mBio 8, e01114–17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. 136.

    Libertucci, J. & Young, V. B. The role of the microbiota in infectious diseases. Nat. Microbiol. 4, 35–45 (2019).

    CAS  PubMed  Google Scholar 

  137. 137.

    Millan, B. et al. Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent Clostridium difficile infection. Clin. Infect. Dis. 62, 1479–1486 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Pamer, E. G. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science 352, 535–538 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. 139.

    Keith, J. W. & Pamer, E. G. Enlisting commensal microbes to resist antibiotic-resistant pathogens. J. Exp. Med. 216, 10–19 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Sorbara, M. T. et al. Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification. J. Exp. Med. 216, 84–98 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Ronda, C., Chen, S. P., Cabral, V., Yaung, S. J. & Wang, H. H. Metagenomic engineering of the mammalian gut microbiome in situ. Nat. Methods 16, 167–170 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142.

    Kang, Y. K. et al. Nonviral genome editing based on a polymer-derivatized CRISPR nanocomplex for targeting bacterial pathogens and antibiotic resistance. Bioconjugate Chem. 28, 957–967 (2017).

    CAS  Google Scholar 

  143. 143.

    Mahnert, A. et al. Man-made microbial resistances in built environments. Nat. Commun. 10, 968 (2019).

    PubMed  PubMed Central  Google Scholar 

  144. 144.

    Martinez, J. L. Antibiotics and antibiotic resistance genes in natural environments. Science 321, 365–367 (2008).

    CAS  PubMed  Google Scholar 

  145. 145.

    van der Grinten, E., Pikkemaat, M. G., van den Brandhof, E. J., Stroomberg, G. J. & Kraak, M. H. Comparing the sensitivity of algal, cyanobacterial and bacterial bioassays to different groups of antibiotics. Chemosphere 80, 1–6 (2010).

    PubMed  Google Scholar 

  146. 146.

    Dias, E., Oliveira, M., Manageiro, V., Vasconcelos, V. & Canica, M. Deciphering the role of cyanobacteria in water resistome: hypothesis justifying the antibiotic resistance (phenotype and genotype) in Planktothrix genus. Sci. Total Environ. 652, 447–454 (2019).

    PubMed  Google Scholar 

  147. 147.

    Yu, Y. et al. Investigation of the removal mechanism of antibiotic ceftazidime by green algae and subsequent microbic impact assessment. Sci. Rep. 7, 4168 (2017).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Livanos, A. E. et al. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice. Nat. Microbiol. 1, 16140 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. 149.

    Raymann, K., Shaffer, Z. & Moran, N. A. Antibiotic exposure perturbs the gut microbiota and elevates mortality in honeybees. PLoS Biol. 15, e2001861 (2017).

    PubMed  PubMed Central  Google Scholar 

  150. 150.

    Jørgensen, P. S., Wernli, D., Folke, C. & Carroll, S. P. Changing antibiotic resistance: sustainability transformation to a pro-microbial planet. Curr. Opin. Env. Sust. 25, 66–76 (2017).

    Google Scholar 

  151. 151.

    Durso, L. M. & Cook, K. L. One health and antibiotic resistance in agroecosystems. EcoHealth (2018).

  152. 152.

    Fisher, B., Turner, R. K. & Morling, P. Defining and classifying ecosystem services for decision making. Ecol. Econ. 68, 643–653 (2009).

    Google Scholar 

  153. 153.

    Faith, D. P. et al. Evosystem services: an evolutionary perspective on the links between biodiversity and human well-being. Curr. Opin. Env. Sust. 2, 66–74 (2010).

    Google Scholar 

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J.L.M. is supported by grants from the Instituto de Salud Carlos III (grant no. RD16/0016/0011)—co-financed by the European Development Regional Fund ‘A Way to Achieve Europe’ (grant no. S2017/BMD-3691); InGEMICS-CM, funded by Comunidad de Madrid (Spain) and European Structural and Investment Funds; and by the Spanish Ministry of Economy and Competitivity (grant no. BIO2017-83128-R). T.M.C. and F.B. are supported by the Joint Programming Initiative on Antimicrobial Resistance (grant nos. ST131 JPIAMR2016-AC16/00036 and JPIAMR2016-AC16/00039), the European Development Regional Fund ‘A Way to Achieve Europe’ for co-funding the Spanish R&D National Plan 2012–2019 (grant nos. P15-1581 and PI18-1942), the CIBER (CIBER in Epidemiology and Public Health; grant no. CB06/02/0053), the Regional Government of Madrid (InGeMICS B2017/BMD-3691) and the Fundación Ramón Areces.

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Hernando-Amado, S., Coque, T.M., Baquero, F. et al. Defining and combating antibiotic resistance from One Health and Global Health perspectives. Nat Microbiol 4, 1432–1442 (2019).

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