Distribution of fluoroquinolones in the two aqueous compartments of Escherichia coli

Ankit Pandeya, Olaniyi Alegun, Yuguang Cai, Yinan Wei

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The double-layered cell envelope of Gram-negative bacteria and active drug efflux present a formidable barrier for antimicrobial compounds to penetrate. Fluoroquinolones are among the few classes of antimicrobials that are clinically useful in the treatment of Gram-negative bacterial infection. Previous studies on fluoroquinolone accumulation measured total bacteria associated compounds, rather than the cytoplasmic accumulation. Fluoroquinolones target the type II topoisomerases in the cytoplasm. Thus, the cytoplasmic accumulation is expected to be more relevant to the potency of the drugs. Here, we fractionated and measured the concentration of nine fluoroquinolone compounds in the periplasm and the cytoplasm of two strains of E. coli cells, a parent strain and its isogenic efflux-deficient tolC knockout strain. The potency of the drugs was determined using the minimum inhibitory concentration (MIC) assay. We found that all fluoroquinolones tested accumulated at much higher concentrations in the periplasm than in the cytoplasm. The periplasmic concentrations were 2–15 folds higher than the cytoplasmic concentration, while the actual distribution ratio varies drastically among the compounds tested. Good correlation between the MIC and the cytoplasmic accumulation, but not whole cell accumulation, was observed using a pair of isogenic wild type and drug-efflux deficient strains.

Original languageEnglish
Article number100849
JournalBiochemistry and Biophysics Reports
Volume24
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors

Keywords

  • Fluoroquinolone
  • Gram-negative bacteria
  • Minimum inhibitory concentration
  • Periplasm accumulation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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