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The antibiotic resistome: the nexus of chemical and genetic diversity

Nature Reviews Microbiology volume 5, pages 175–186 (2007)Cite this article

Key Points

  • The antibiotic resistome is the collection of all the antibiotic resistance genes, including those usually associated with pathogenic bacteria isolated in the clinics, non-pathogenic antibiotic producing bacteria and all other resistance genes.

  • Many bacterial genomes contain cryptic resistance genes that can confer resistance, but do not seem to have been selected in response to recent exposure to antibiotics. These represent a large reservoir of antibiotic resistance genes.

  • The antibiotic resistance genes in environmental and other non-pathogenic bacteria share amino-acid sequence similarities and biochemical mechanisms with resistance elements in clinical isolates.

  • Structural biology and protein biochemistry has revealed that antibiotic resistance has evolved from precursor proteins with other metabolic functions. The powerful selection pressure produced by the use of cytotoxic antimicrobial agents spurs the selection of resistance mechanisms from these precursors.

  • Antibiotics are ancient, dating back hundreds of millions of years. Resistance is therefore equally ancient, and the number of genes in the resistome is a reflection of the continuous co-evolution of small molecules in natural environments and microbial genomes.

Abstract

Over the millennia, microorganisms have evolved evasion strategies to overcome a myriad of chemical and environmental challenges, including antimicrobial drugs. Even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Moreover, the potential problem of the widespread distribution of antibiotic resistant bacteria was recognized by scientists and healthcare specialists from the initial use of these drugs. Why is resistance inevitable and where does it come from? Understanding the molecular diversity that underlies resistance will inform our use of these drugs and guide efforts to develop new efficacious antibiotics.

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Figure 1: The antibiotic resistome.
Figure 2: Streptogramin antibiotics and streptogramin resistance.
Figure 3: Genome context of chromosomal antibiotic resistance genes.
Figure 4: Vancomycin resistance: an elegant mechanism of antibiotic evasion.
Figure 5: Vancomycin-resistance genes are widespread in the environment.
Figure 6: Evolution of antibiotic resistance proteins.

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Acknowledgements

The author's research in antibiotic resistance is supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and a Canada Research Chair in Antibiotic Biochemistry.

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  1. Department of Biochemistry and Biomedical Sciences, Antimicrobial Research Centre, DeGroote School of Medicine, McMaster University, 1200 Main Street West Hamilton, Ontario, L8N 3Z5, Canada

    Gerard D. Wright

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DATABASES

Entrez Genome Project

Acinetobacter baumannii

Bordetella pertussis

Burkholderia cepacia

Escherichia coli

Klebsiella pneumoniae

Legionella pneumophila

Mycobacterium smegmatis

Mycobacterium tuberculosis

Pseudomonas aeruginosa

Salmonella enterica serovar Typhimurium

Staphylococcus aureus

Stenotrophomonas maltophilia

Streptococcus pneumoniae

Streptomyces avermitilis

Streptomyces coelicolor

Yersinia enterocolitica

FURTHER INFORMATION

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Glossary

Superbug

A bacterial pathogen that is resistant to multiple antibiotics.

Resistome

A collection of all the antibiotic resistance genes and their precursors in pathogenic and non-pathogenic bacteria.

Cryptic resistance gene

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

R-plasmid

A plasmid that is present in bacterial pathogens and environmental microorganisms, and that contains one or more antibiotic resistance genes.

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Wright, G. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol 5, 175–186 (2007). https://doi.org/10.1038/nrmicro1614

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