Drug detoxification dynamics explain the postantibiotic effect.

Published

Journal Article

The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical observations, a mechanistic understanding of this phenomenon is lacking. Using a combination of modeling and quantitative experiments, we show that the PAE can be explained by the temporal dynamics of drug detoxification in individual cells after an antibiotic is removed from the extracellular environment. These dynamics are dictated by both the export of the antibiotic and the intracellular titration of the antibiotic by its target. This mechanism is generally applicable for antibiotics with different modes of action. We further show that efflux inhibition is effective against certain antibiotic motifs, which may help explain mixed cotreatment success.

Full Text

Duke Authors

Cited Authors

  • Srimani, JK; Huang, S; Lopatkin, AJ; You, L

Published Date

  • October 23, 2017

Published In

Volume / Issue

  • 13 / 10

Start / End Page

  • 948 -

PubMed ID

  • 29061668

Pubmed Central ID

  • 29061668

Electronic International Standard Serial Number (EISSN)

  • 1744-4292

International Standard Serial Number (ISSN)

  • 1744-4292

Digital Object Identifier (DOI)

  • 10.15252/msb.20177723

Language

  • eng