A Fluorescent Probe Distinguishes between Inhibition of Early and Late Steps of Lipopolysaccharide Biogenesis in Whole Cells

Eileen Moison, Ran Xie, Ge Zhang, Matthew D. Lebar, Timothy C. Meredith, Daniel Kahne

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Lipopolysaccharide (LPS) biogenesis in Gram-negative organisms involves its biosynthesis in the cytoplasm and subsequent transport across three cellular compartments to the cell surface. We developed a fluorescent probe that allows us to determine the spatial distribution of LPS in whole cells. We show that polymyxin B nonapeptide (PMBN) containing a dansyl fluorophore specifically binds to LPS in membranes. We show that this probe detects decreases in LPS levels on the cell surface when LPS biosynthesis is inhibited at an early step. We also can detect accumulation of LPS in particular subcellular locations when LPS assembly is blocked during transport, allowing us to differentiate inhibitors targeting early and late stages of LPS biogenesis.

Original languageEnglish (US)
Pages (from-to)928-932
Number of pages5
JournalACS chemical biology
Volume12
Issue number4
DOIs
StatePublished - Apr 21 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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