Abstract

Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities. We found that resistomes across habitats are generally structured by bacterial phylogeny along ecological gradients, but identified key resistance genes that cross habitat boundaries and determined their association with mobile genetic elements. We also assessed the effectiveness of widely used excreta management strategies in reducing faecal bacteria and resistance genes in these settings representative of low- and middle-income countries. Our results lay the foundation for quantitative risk assessment and surveillance of resistance gene dissemination across interconnected habitats in settings representing over two-thirds of the world’s population.

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Acknowledgements

We thank the residents of our study communities in El Salvador and Peru for their generosity and trust, without which this study would not have been possible; Epilogos Charities Inc. for on-site logistical support and community networking; the Fundación Luis Edmundo Vásquez (FUNDALEV), Universidad Dr. José Matías Delgado, Asociación Benéfica Prisma, and Universidad Peruana Cayetano Heredia for logistical support in the collection and shipment of samples; S. del Pilar Basilio at SEDAPAL in Lima for facilitating access and sample collection at the ‘PTAR San Juan’ WWTP; J. Hoisington-Lopez at the Center for Genome Sciences and Systems Biology and staff at the Genome Technology Access Center at Washington University School of Medicine for generating Illumina sequencing data; S. Alvarez and staff at the Proteomics & Mass Spectrometry Facility at the Donald Danforth Plant Science Center for mass-spectrometry analyses of water samples; and members of the Dantas laboratory for discussions of the results and analyses. This work is supported in part by awards to G.D. through the Edward Mallinckrodt, Jr. Foundation (Scholar Award), the Children’s Discovery Institute (MD-II-2011-117), and the National Institute of General Medical Sciences of the National Institutes of Health (R01-GM099538). Work at the DDPSC was supported by the National Science Foundation (DBI-0521250) for acquisition of the QTRAP LC-MS/MS instrument. E.C.P. is funded by the Department of Defense (DoD) through the National Defense Science and Engineering Graduate (NDSEG) Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Author information

Author notes

    • Erica C. Pehrsson
    •  & Pablo Tsukayama

    These authors contributed equally to this work.

Affiliations

  1. Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Erica C. Pehrsson
    • , Pablo Tsukayama
    • , Sanket Patel
    • , Melissa Mejía-Bautista
    • , Giordano Sosa-Soto
    •  & Gautam Dantas
  2. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Sanket Patel
    •  & Gautam Dantas
  3. Facultad de Ciencias de la Salud “Dr. Luis Edmundo Vásquez”, Universidad Dr. José Matías Delgado, El Salvador

    • Melissa Mejía-Bautista
    • , Giordano Sosa-Soto
    • , Karla M. Navarrete
    • , William Hoyos-Arango
    •  & M. Teresita Bertoli
  4. Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, San Martin de Porres, Lima 31, Peru

    • Maritza Calderon
    •  & Robert H. Gilman
  5. Asociacion Benéfica PRISMA, San Miguel, Lima 32, Peru

    • Lilia Cabrera
    •  & Robert H. Gilman
  6. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Douglas E. Berg
    •  & Gautam Dantas
  7. Department of Medicine, University of California San Diego, La Jolla, California 92093, USA

    • Douglas E. Berg
  8. Department of International Health, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA

    • Robert H. Gilman
  9. Department of Biomedical Engineering, Washington University, St Louis, Missouri 63105, USA

    • Gautam Dantas

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Contributions

D.E.B., G.D., M.T.B., and E.C.P. planned the RES study; D.E.B., G.D., R.H.G., and P.T. planned the PST study; M.T.B. and W.H.A. implemented the RES study approval in El Salvador; E.C.P. implemented the RES study approval in the USA; R.H.G. and L.C. implemented the PST study approval in Peru; P.T. implemented the PST study approval in the USA; M.T.B., W.H.A., K.M.N., M.M.B., G.S.S., and E.C.P. collected surveys and samples in RES; P.T., M.C., and L.C. collected samples in PST; E.C.P., M.M.B., G.S.S., and S.P. extracted DNA and generated 16S, functional metagenomic, and shotgun data for RES samples; P.T. and S.P. extracted DNA and generated 16S, functional metagenomic, and shotgun data for PST samples; E.C.P. and P.T. performed analyses and interpreted results; and E.C.P., P.T., and G.D. wrote the paper with input from other co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gautam Dantas.

Assembled functional metagenomic contigs and 16S and shotgun metagenomic reads have been deposited to NCBI GenBank and SRA (PRJNA300541).

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https://doi.org/10.1038/nature17672

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