1. Sci Rep. 2017 Sep 6;7(1):10697. doi: 10.1038/s41598-017-10543-3.

Targeting Bacterial Cardiolipin Enriched Microdomains: An Antimicrobial Strategy 
Used by Amphiphilic Aminoglycoside Antibiotics.

El Khoury M(1), Swain J(1), Sautrey G(1)(2), Zimmermann L(3), Van Der Smissen
P(4), Décout JL(3), Mingeot-Leclercq MP(5).

Author information: 
(1)Université catholique de Louvain, Louvain Drug Research Institute,
Pharmacologie Cellulaire et Moléculaire, avenue E. Mounier 73, UCL B1.73.05,
1200, Brussels, Belgium.
(2)Université de Lorraine, UMR CNRS UL 7565, 1 Blvd. Des Aiguillettes, BP 70239, 
54506 Vandoeuvre-lès-Nancy Cedex, Nancy, France.
(3)Université Grenoble Alpes, Joseph Fourier/CNRS, Institut de Pharmacochimie
Moléculaire, rue de la Chimie, F-38041, Grenoble, France.
(4)Université Catholique de Louvain, de Duve Institute, avenue Hippocrate 75, UCL
B1.75.05, 1200, Brussels, Belgium.
(5)Université catholique de Louvain, Louvain Drug Research Institute,
Pharmacologie Cellulaire et Moléculaire, avenue E. Mounier 73, UCL B1.73.05,
1200, Brussels, Belgium. marie-paule.mingeot@uclouvain.be.

Some bacterial proteins involved in cell division and oxidative phosphorylation
are tightly bound to cardiolipin. Cardiolipin is a non-bilayer anionic
phospholipid found in bacterial inner membrane. It forms lipid microdomains
located at the cell poles and division plane. Mechanisms by which microdomains
are affected by membrane-acting antibiotics and the impact of these alterations
on membrane properties and protein functions remain unclear. In this study, we
demonstrated cardiolipin relocation and clustering as a result of exposure to a
cardiolipin-acting amphiphilic aminoglycoside antibiotic, the 3',6-dinonyl
neamine. Changes in the biophysical properties of the bacterial membrane of P.
aeruginosa, including decreased fluidity and increased permeability, were
observed. Cardiolipin-interacting proteins and functions regulated by cardiolipin
were impacted by the amphiphilic aminoglycoside as we demonstrated an inhibition 
of respiratory chain and changes in bacterial shape. The latter effect was
characterized by the loss of bacterial rod shape through a decrease in length and
increase in curvature. It resulted from the effect on MreB, a cardiolipin
dependent cytoskeleton protein as well as a direct effect of 3',6-dinonyl neamine
on cardiolipin. These results shed light on how targeting cardiolipin
microdomains may be of great interest for developing new antibacterial therapies.

DOI: 10.1038/s41598-017-10543-3 
PMCID: PMC5587548
PMID: 28878347