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Antibiotic interactions that select against resistance

Author

Listed:
  • Remy Chait

    (Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA)

  • Allison Craney

    (Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA)

  • Roy Kishony

    (Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA)

Abstract

Resistance movement It's the 'catch-22' of antimicrobial treatments: the use of any drug inherently generates selection for resistant mutants. But a new study has come up with a result that holds out the tantalizing prospect that it might be possible to bias selection against resistance. Sensitive growth rate measurements and competition assays between drug-sensitive and drug-resistant strains were performed for a range of combined drug dosages. At certain sublethal concentrations, a mixture of doxycycline and ciprofloxacin preferentially selected for wild-type Escherichia coli in favour of a resistant strain in a lab culture. This paradox can be understood theoretically by a simple geometrical argument. Sublethal concentrations, of course, are not clinically relevant, but this work does suggest that further research might lead to antimicrobial combinations with improved selection against resistance.

Suggested Citation

  • Remy Chait & Allison Craney & Roy Kishony, 2007. "Antibiotic interactions that select against resistance," Nature, Nature, vol. 446(7136), pages 668-671, April.
  • Handle: RePEc:nat:nature:v:446:y:2007:i:7136:d:10.1038_nature05685
    DOI: 10.1038/nature05685
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    Citations

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    Cited by:

    1. Eva Stadler & Mohamed Maiga & Lukas Friedrich & Vandana Thathy & Claudia Demarta-Gatsi & Antoine Dara & Fanta Sogore & Josefine Striepen & Claude Oeuvray & Abdoulaye A. Djimdé & Marcus C. S. Lee & Lau, 2023. "Propensity of selecting mutant parasites for the antimalarial drug cabamiquine," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Roger Guimerà & Marta Sales-Pardo, 2013. "A Network Inference Method for Large-Scale Unsupervised Identification of Novel Drug-Drug Interactions," PLOS Computational Biology, Public Library of Science, vol. 9(12), pages 1-9, December.
    3. Jeff Maltas & Kevin B Wood, 2019. "Pervasive and diverse collateral sensitivity profiles inform optimal strategies to limit antibiotic resistance," PLOS Biology, Public Library of Science, vol. 17(10), pages 1-34, October.
    4. Chih-Wei Chen & Nadja Leimer & Egor A. Syroegin & Clémence Dunand & Zackery P. Bulman & Kim Lewis & Yury S. Polikanov & Maxim S. Svetlov, 2023. "Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Elsa Hansen & Jason Karslake & Robert J Woods & Andrew F Read & Kevin B Wood, 2020. "Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations," PLOS Biology, Public Library of Science, vol. 18(5), pages 1-20, May.
    6. Marianne Bauer & Isabella R Graf & Vudtiwat Ngampruetikorn & Greg J Stephens & Erwin Frey, 2017. "Exploiting ecology in drug pulse sequences in favour of population reduction," PLOS Computational Biology, Public Library of Science, vol. 13(9), pages 1-17, September.
    7. Joseph Peter Torella & Remy Chait & Roy Kishony, 2010. "Optimal Drug Synergy in Antimicrobial Treatments," PLOS Computational Biology, Public Library of Science, vol. 6(6), pages 1-9, June.
    8. Daniel Nichol & Peter Jeavons & Alexander G Fletcher & Robert A Bonomo & Philip K Maini & Jerome L Paul & Robert A Gatenby & Alexander RA Anderson & Jacob G Scott, 2015. "Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance," PLOS Computational Biology, Public Library of Science, vol. 11(9), pages 1-19, September.
    9. Greenspoon, Philip B. & Mideo, Nicole, 2017. "Evolutionary rescue of a parasite population by mutation rate evolution," Theoretical Population Biology, Elsevier, vol. 117(C), pages 64-75.
    10. Philip Gerlee & Linnéa Schmidt & Naser Monsefi & Teresia Kling & Rebecka Jörnsten & Sven Nelander, 2013. "Searching for Synergies: Matrix Algebraic Approaches for Efficient Pair Screening," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-10, July.

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