Review Article | Published:

Next-generation approaches to understand and combat the antibiotic resistome

Nature Reviews Microbiology volume 15, pages 422434 (2017) | Download Citation

Abstract

Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.

Key points

  • The anthropogenic use of antibiotics has selected for an increase in the evolution and dissemination of antibiotic resistance in environmental and human-associated bacteria.

  • The first generation of antibiotic resistance research coincided with the golden age of antibiotics and focused on single resistance genes in single (usually pathogenic) organisms.

  • In recent decades, technical and computational advances in genomics and metagenomics have revealed widespread resistance across diverse microbial communities.

  • Recent exceptional studies integrate a deep mechanistic understanding of resistance determinants with broad genomic analysis of microorganisms and microbial communities to improve both the surveillance of resistance threats and the proactive development of strategies to counter these threats.

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Acknowledgements

This work was supported, in part, by awards to G.D. through the Edward Mallinckrodt Jr. Foundation (Scholar Award), and from the US National Institutes of Health (NIH) Director's New Innovator Award (http://commonfund.nih.gov/newinnovator/), the National Institute of Diabetes and Digestive and Kidney Diseases (http://www.niddk.nih.gov/), the National Institute of General Medical Sciences (NIGMS; http://www.nigms.nih.gov/) and the National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov/) of the NIH under award numbers DP2DK098089, R01GM099538 and R01AI123394, respectively. T.S.C. received support from a National Institute of Child Health and Development training grant through award number T32 HD049305 (K. H. Moley is named as the Principal Investigator on this grant). A.J.G. received support from a NIGMS training grant through award number T32 GM007067 (J. Skeath is named as the Principal Investigator on this grant). The content of this Review is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Author information

Author notes

    • Terence S. Crofts
    •  & Andrew J. Gasparrini

    These authors contributed equally to this work.

Affiliations

  1. Center for Genome Sciences & Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, Missouri 63110, USA.

    • Terence S. Crofts
    • , Andrew J. Gasparrini
    •  & Gautam Dantas
  2. Department of Pathology and Immunology, Washington University School of Medicine.

    • Gautam Dantas
  3. Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.

    • Gautam Dantas
  4. Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Drive, St. Louis, Missouri 63130, USA.

    • Gautam Dantas

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Gautam Dantas.

Supplementary information

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  1. 1.

    Supplementary information S1

    Supplementary information S1 (table)

Glossary

Antibiotics

Drugs that inhibit the growth of bacteria or kill them.

Natural products

Small molecules that are naturally produced by living organisms.

Proto-resistance genes

Genes that have the potential to evolve a resistance function.

Cryptic resistance genes

A resistance gene that is embedded in a bacterial chromosome, but that is not obviously associated with antibiotic resistance. The respective gene is usually either not expressed or expressed at low levels.

Metagenomes

The collective genetic material in a given environment.

Synteny

The occurrence of multiple genes in the same genetic locus.

Horizontal gene transfer

The transmission of genetic material between bacterial organisms by transformation, transduction or conjugation, in contrast to vertical transmission through heredity.

Axenic

A term that describes a culture that contains only a single species.

Koch's postulates

A series of criteria proposed by Robert Koch in 1890 that can be used to establish a causal relationship between a microorganism and a disease.

Collaterally sensitive

A term that describes organisms that develop resistance to one antibiotic and, as a result of the new mutation, are more sensitive to another antibiotic.

PCR

A molecular biology technique that is used to amplify nucleic acids of known sequence.

Whole-genome sequencing

(WGS). The use of next-generation sequencing to determine the complete sequence of an organism's genome.

Hidden Markov models

Statistical models that are widely used in biological sequence analysis and annotation.

Semi-synthetic

A term that describes a small molecule that is produced by chemical modification of a natural product.

Next-generation sequencing

High-throughput nucleic acid sequencing technologies that have emerged in the past few decades to enable substantial increases in sequencing capacity.

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DOI

https://doi.org/10.1038/nrmicro.2017.28

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