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The evolution of heteroresistance via small colony variants in Escherichia coli following long term exposure to bacteriostatic antibiotics

Author

Listed:
  • Teresa Gil-Gil

    (Emory University)

  • Brandon A. Berryhill

    (Emory University
    Emory University)

  • Joshua A. Manuel

    (Emory University)

  • Andrew P. Smith

    (Emory University)

  • Ingrid C. McCall

    (Emory University)

  • Fernando Baquero

    (Epidemiología y Salud Pública (CIBERESP))

  • Bruce R. Levin

    (Emory University)

Abstract

Traditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics of Escherichia coli after exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days. The results of our experiments provide evidence that bacteria exposed to these drugs replicate, evolve, and generate a sub-population of small colony variants (SCVs) which are resistant to multiple drugs. These SCVs contribute to the evolution of heteroresistance and rapidly revert to a susceptible state once the antibiotic is removed. Stated another way, exposure to bacteriostatic drugs selects for the evolution of heteroresistance in populations previously lacking this trait. More generally, our results question the definition of bacteriostasis as populations exposed to bacteriostatic drugs are replicating despite the lack of net growth.

Suggested Citation

  • Teresa Gil-Gil & Brandon A. Berryhill & Joshua A. Manuel & Andrew P. Smith & Ingrid C. McCall & Fernando Baquero & Bruce R. Levin, 2024. "The evolution of heteroresistance via small colony variants in Escherichia coli following long term exposure to bacteriostatic antibiotics," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52166-z
    DOI: 10.1038/s41467-024-52166-z
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    References listed on IDEAS

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    1. Iskander Khusainov & Natalie Romanov & Camille Goemans & Beata Turoňová & Christian E. Zimmerli & Sonja Welsch & Julian D. Langer & Athanasios Typas & Martin Beck, 2024. "Bactericidal effect of tetracycline in E. coli strain ED1a may be associated with ribosome dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
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