Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Innovation
  • Published:

Predicting the evolution of antibiotic resistance genes

Nature Reviews Microbiology volume 2, pages 430–435 (2004)Cite this article

Abstract

Antibiotic resistance is thought to evolve rapidly in response to antibiotic use. At present, we lack effective tools to assess how rapidly existing resistance genes are likely to evolve to yield resistance to newly introduced drugs. To address this problem, a method has been developed for in vitro evolution experiments to help predict how long it will take antibiotic resistance to arise — potentially allowing informed decisions about usage to be made.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The Barlow–Hall method of in vitro evolution to predict in vivo evolution.
Figure 2: The GeneHunter method for identifying and isolating cryptic antibiotic-resistance genes.

Similar content being viewed by others

References

  1. Palumbi, S. R. Humans as the world's greatest evolutionary force. Science 293, 1786–1790 (2001).

    Article  CAS  Google Scholar 

  2. Harrison, P. F. & Lederberg, J. (eds) Antimicrobial Resistance: Issues and Options (National Academy Press, Washington DC, 1998).

    Google Scholar 

  3. Interagency Task Force on Antimicrobial Resistance. A public health action plan to combat antimicrobial resistance. [online], <http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf> (1999).

  4. National Antimicrobial Resistance Monitoring System Annual Report 2000 [online], <http://www.cdc.gov/narms/annual/2000/narms_2000_annual_a.htm> (2000).

  5. Walsh, C. Where will new antibiotics come from? Nature Rev. Microbiol. 1, 65–70 (2003).

    Article  CAS  Google Scholar 

  6. Hall, R. M. & Stokes, H. W. Integrons: novel DNA elements which capture genes by site-specific recombination. Genetica 90, 115–132 (1993).

    Article  CAS  Google Scholar 

  7. Livermore, D. Can better prescribing turn the tide of resistance? Nature Rev. Microbiol. 2, 73–78 (2004).

    Article  CAS  Google Scholar 

  8. CDC Interagency Public Health Action Plan 2001 Annual Report [online], <http://www.cdc.gov/drugresistance/actionplan/2001report/index.htm> (2001).

  9. Galewitz, P. Pharmacia and Upjohn readies new antibiotic. [online], <http://www.louisville.edu/~rmatla01/discus/messages/161/161.html> (1999).

  10. Stemmer, W. P. C. Rapid evolution of a protein in vitro by DNA shuffling. Nature 370, 389–390 (1994).

    Article  CAS  Google Scholar 

  11. Barlow, M. & Hall, B. G. Predicting evolutionary potential: in vitro evolution accurately reproduces natural evolution of the TEM β-lactamase. Genetics 160, 823–832 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Barlow, M. & Hall, B. G. Experimental prediction of the natural evolution of antibiotic resistance. Genetics 163, 1237–1241 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Barlow, M. & Hall, B. G. Experimental prediction of the evolution of cefepime resistance from the CMY-2 AmpC β-lactamase. Genetics 164, 23–29 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Salipante, S. J. & Hall, B. G. Determining the limits of the evolutionary potential of an antibiotic resistance gene. Mol. Biol. Evol. 20, 653–659 (2003).

    Article  CAS  Google Scholar 

  15. Hall, B. G. In vitro evolution predicts that the IMP-1 metallo-β-lactamase does not have the potential to evolve increased activity toward imipenem. Antimicrob. Agents Chemother. 48, 1032–1033 (2004).

    Article  CAS  Google Scholar 

  16. Barlow, M. & Hall, B. G. Origin and evolution of the AmpC β-lactamases of Citrobacter freundii. Antimicrob. Agents Chemother. 46, 1190–1198 (2002).

    Article  CAS  Google Scholar 

  17. Barlow, M. & Hall, B. G. Phylogenetic analysis shows that the OXA β-lactamase genes have been on plasmids for millions of years. J. Mol. Evol. 55, 314–321 (2002).

    Article  CAS  Google Scholar 

  18. Hall, B. G., Salipante, S. J. & Barlow, M. The metallo-β-lactamases fall into two distinct phylogenetic groups. J. Mol. Evol. 57, 249–254 (2003).

    Article  CAS  Google Scholar 

  19. Hall, B. G. & Barlow, M. Structure-based phylogenies of the serine β-lactamases. J. Mol. Evol. 57, 255–260 (2003).

    Article  CAS  Google Scholar 

  20. Hall, B. G., Salipante, S. J. & Barlow, M. Independent origins of the subgroup (B1 + B2) and the subgroup B3 metallo-β-lactamases. J. Mol. Evol. (in the press).

  21. Magnet, S., Courvalin, P. & Lambert, T. Activation of the cryptic aac(6′)-Iy aminoglycoside resistance gene of Salmonella by a chromosomal deletion generating a transcriptional fusion. J. Bacteriol. 181, 6650–6655 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Podglajen, I., Breuil, J., Bordon, F., Gutmann, L. & Collatz, E. A silent carbapenemase gene in strains of Bacteroides fragilis can be expressed after a one-step mutation. FEMS Microbiol. Lett. 70, 21–29 (1992).

    Article  CAS  Google Scholar 

  23. Salipante, S. J., Barlow, M. & Hall, B. G. GeneHunter: a transposon tool for the identification and isolation of cryptic antibiotic resistance genes. Antimicrob. Agents. Chemother. 47, 3840–3845 (2004).

    Article  Google Scholar 

Download references

Acknowledgements

The author's studies were supported by a grant from the National Institutes of Health.

Author's note

The computer program 'InVitro Evolution Simulator' is available free of charge on e-mail request to the author.

Author information

Author notes

  1. Barry G. Hall

    Present address: , 218 Chuckanut Point Road, Bellingham, 98229, Washington, USA

Authors and Affiliations

  1. Biology Department, University of Rochester, USA

    Barry G. Hall

Authors
  1. Barry G. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

DATABASES

Entrez

Bacillus cereus

Staphylococcus aureus

Streptococcus pneumoniae

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hall, B. Predicting the evolution of antibiotic resistance genes. Nat Rev Microbiol 2, 430–435 (2004). https://doi.org/10.1038/nrmicro888

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro888

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing