1. PLoS One. 2018 Aug 20;13(8):e0201752. doi: 10.1371/journal.pone.0201752.
eCollection 2018.

Effect of cardiolipin on the antimicrobial activity of a new amphiphilic
aminoglycoside derivative on Pseudomonas aeruginosa.

Swain J(1), El Khoury M(1), Kempf J(2), Briée F(2), Van Der Smissen P(3), Décout 
JL(2), Mingeot-Leclercq MP(1).

Author information: 
(1)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium.
(2)Département de Pharmacochimie Moléculaire, Université Grenoble Alpes, CNRS,
Grenoble, France.
(3)de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

Amphiphilic aminoglycoside derivatives are promising new antibacterials active
against Gram-negative bacteria such as Pseudomonas aeruginosa, including colistin
resistant strains. In this study, we demonstrated that addition of cardiolipin to
the culture medium delayed growth of P. aeruginosa, favored asymmetrical growth
and enhanced the efficiency of a new amphiphilic aminoglycoside derivative, the
3',6-dinonylneamine. By using membrane models mimicking P. aeruginosa plasma
membrane composition (POPE:POPG:CL), we demonstrated the ability of
3'6-dinonylneamine to induce changes in the biophysical properties of membrane
model lipid systems in a cardiolipin dependent manner. These changes include an
increased membrane permeability associated with a reduced hydration and a
decreased ability of membrane to mix and fuse as shown by monitoring calcein
release, Generalized Polarization of Laurdan and fluorescence dequenching of
octadecyl rhodamine B, respectively. Altogether, results shed light on how
cardiolipin may be critical for improving antibacterial action of new amphiphilic
aminoglycoside derivatives.

DOI: 10.1371/journal.pone.0201752 
PMID: 30125281 

Conflict of interest statement: The authors have declared that no competing
interests exist.