Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization

Biomolecules. 2020 Feb 15;10(2):309. doi: 10.3390/biom10020309.

Abstract

Appending a lipophylic alkyl chain by ester bond to fluorescein has been previously shown to convert this popular dye into an effective protonophoric uncoupler of oxidative phosphorylation in mitochondria, exhibiting neuro- and nephroprotective effects in murine models. In line with this finding, we here report data on the pronounced depolarizing effect of a series of fluorescein decyl esters on bacterial cells. The binding of the fluorescein derivatives to Bacillus subtilis cells was monitored by fluorescence microscopy and fluorescence correlation spectroscopy (FCS). FCS revealed the energy-dependent accumulation of the fluorescein esters with decyl(triphenyl)- and decyl(tri-p-tolyl)phosphonium cations in the bacterial cells. The latter compound proved to be the most potent in suppressing B. subtilis growth.

Keywords: antibacterial agent; bacterial membrane depolarization; fluorescein derivative; fluorescent uncoupler; membrane potential; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / metabolism
  • Bacterial Outer Membrane / drug effects*
  • Fluorescein / metabolism
  • Fluorescein / pharmacology*
  • Mitochondria / metabolism
  • Mitochondria, Liver / metabolism
  • Oxidative Phosphorylation / drug effects
  • Rats
  • Russia
  • Spectrometry, Fluorescence / methods

Substances

  • Anti-Bacterial Agents
  • Fluorescein