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Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate.

Publication ,  Journal Article
Lopatkin, AJ; Stokes, JM; Zheng, EJ; Yang, JH; Takahashi, MK; You, L; Collins, JJ
Published in: Nature microbiology
December 2019

Growth rate and metabolic state of bacteria have been separately shown to affect antibiotic efficacy1-3. However, the two are interrelated as bacterial growth inherently imposes a metabolic burden4; thus, determining individual contributions from each is challenging5,6. Indeed, faster growth is often correlated with increased antibiotic efficacy7,8; however, the concurrent role of metabolism in that relationship has not been well characterized. As a result, a clear understanding of the interdependence between growth and metabolism, and their implications for antibiotic efficacy, are lacking9. Here, we measured growth and metabolism in parallel across a broad range of coupled and uncoupled conditions to determine their relative contribution to antibiotic lethality. We show that when growth and metabolism are uncoupled, antibiotic lethality uniformly depends on the bacterial metabolic state at the time of treatment, rather than growth rate. We further reveal a critical metabolic threshold below which antibiotic lethality is negligible. These findings were general for a wide range of conditions, including nine representative bactericidal drugs and a diverse range of Gram-positive and Gram-negative species (Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus). This study provides a cohesive metabolic-dependent basis for antibiotic-mediated cell death, with implications for current treatment strategies and future drug development.

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Published In

Nature microbiology

DOI

EISSN

2058-5276

ISSN

2058-5276

Publication Date

December 2019

Volume

4

Issue

12

Start / End Page

2109 / 2117

Related Subject Headings

  • Models, Theoretical
  • Microbial Viability
  • Microbial Sensitivity Tests
  • Gram-Positive Bacteria
  • Gram-Negative Bacteria
  • Anti-Bacterial Agents
  • 3107 Microbiology
  • 1108 Medical Microbiology
  • 0605 Microbiology
 

Citation

APA
Chicago
ICMJE
MLA
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Lopatkin, A. J., Stokes, J. M., Zheng, E. J., Yang, J. H., Takahashi, M. K., You, L., & Collins, J. J. (2019). Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate. Nature Microbiology, 4(12), 2109–2117. https://doi.org/10.1038/s41564-019-0536-0
Lopatkin, Allison J., Jonathan M. Stokes, Erica J. Zheng, Jason H. Yang, Melissa K. Takahashi, Lingchong You, and James J. Collins. “Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate.Nature Microbiology 4, no. 12 (December 2019): 2109–17. https://doi.org/10.1038/s41564-019-0536-0.
Lopatkin AJ, Stokes JM, Zheng EJ, Yang JH, Takahashi MK, You L, et al. Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate. Nature microbiology. 2019 Dec;4(12):2109–17.
Lopatkin, Allison J., et al. “Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate.Nature Microbiology, vol. 4, no. 12, Dec. 2019, pp. 2109–17. Epmc, doi:10.1038/s41564-019-0536-0.
Lopatkin AJ, Stokes JM, Zheng EJ, Yang JH, Takahashi MK, You L, Collins JJ. Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate. Nature microbiology. 2019 Dec;4(12):2109–2117.

Published In

Nature microbiology

DOI

EISSN

2058-5276

ISSN

2058-5276

Publication Date

December 2019

Volume

4

Issue

12

Start / End Page

2109 / 2117

Related Subject Headings

  • Models, Theoretical
  • Microbial Viability
  • Microbial Sensitivity Tests
  • Gram-Positive Bacteria
  • Gram-Negative Bacteria
  • Anti-Bacterial Agents
  • 3107 Microbiology
  • 1108 Medical Microbiology
  • 0605 Microbiology