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Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization.

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.

SUBMITTER: Nazarov PA

PROVIDER: S-EPMC7072581 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization.

Nazarov Pavel A PA Kirsanov Roman S RS Denisov Stepan S SS Khailova Ljudmila S LS Karakozova Marina V MV Lyamzaev Konstantin G KG Korshunova Galina A GA Lukyanov Konstantin A KA Kotova Elena A EA Antonenko Yuri N YN

Biomolecules 20200215 2

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 <i>Bacillus subtilis</i> cells was mon ...[more]

PMID: 32075319

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Project description:This study presents an investigation of pacemaker mechanisms underlying lymphatic vasomotion. We tested the hypothesis that active inositol 1,4,5-trisphosphate receptor (IP(3)R)-operated Ca(2+) stores interact as coupled oscillators to produce near-synchronous Ca(2+) release events and associated pacemaker potentials, this driving action potentials and constrictions of lymphatic smooth muscle. Application of endothelin 1 (ET-1), an agonist known to enhance synthesis of IP(3), to quiescent lymphatic smooth muscle syncytia first enhanced spontaneous Ca(2+) transients and/or intracellular Ca(2+) waves. Larger near-synchronous Ca(2+) transients then occurred leading to global synchronous Ca(2+) transients associated with action potentials and resultant vasomotion. In contrast, blockade of L-type Ca(2+) channels with nifedipine prevented ET-1 from inducing near-synchronous Ca(2+) transients and resultant action potentials, leaving only asynchronous Ca(2+) transients and local Ca(2+) waves. These data were well simulated by a model of lymphatic smooth muscle with: 1), oscillatory Ca(2+) release from IP(3)R-operated Ca(2+) stores, which causes depolarization; 2), L-type Ca(2+) channels; and 3), gap junctions between cells. Stimulation of the stores caused global pacemaker activity through coupled oscillator-based entrainment of the stores. Membrane potential changes and positive feedback by L-type Ca(2+) channels to produce more store activity were fundamental to this process providing long-range electrochemical coupling between the Ca(2+) store oscillators. We conclude that lymphatic pacemaking is mediated by coupled oscillator-based interactions between active Ca(2+) stores. These are weakly coupled by inter- and intracellular diffusion of store activators and strongly coupled by membrane potential. Ca(2+) store-based pacemaking is predicted for cellular systems where: 1), oscillatory Ca(2+) release induces depolarization; 2), membrane depolarization provides positive feedback to induce further store Ca(2+) release; and 3), cells are interconnected. These conditions are met in a surprisingly large number of cellular systems including gastrointestinal, lymphatic, urethral, and vascular tissues, and in heart pacemaker cells.

Dataset Information

Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization.

Publications

Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization.

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