Intact cell lipidomics reveal changes to the ratio of cardiolipins to phosphatidylinositols in response to kanamycin in HeLa and primary cells

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Title: Intact cell lipidomics reveal changes to the ratio of cardiolipins to phosphatidylinositols in response to kanamycin in HeLa and primary cells
Author(s): Larrouy-Maumus, GJ
Mostowy, S
Lobato-Márquez, D
Thomson, M
Pennisi, I
Krokowski, S
Item Type: Journal Article
Abstract: Antimicrobial resistance is a major threat the world is currently facing. Development of new antibiotics and the assessment of their toxicity represent important challenges. Current methods for addressing antibiotic toxicity rely on measuring mitochondrial damage using ATP and/or membrane potential as a readout. In this study, we propose an alternative readout looking at changes in the lipidome on intact and unprocessed cells by matrix-assisted laser desorption ionization mass spectrometry. As a proof of principle, we evaluated the impact of known antibiotics (levofloxacin, ethambutol, and kanamycin) on the lipidome of HeLa cells and mouse bone marrow-derived macrophages. Our methodology revealed that clinically relevant concentrations of kanamycin alter the ratio of cardiolipins to phosphatidylinositols. Unexpectedly, only kanamycin had this effect even though all antibiotics used in this study led to a decrease in the maximal mitochondrial respiratory capacity. Altogether, we report that intact cell-targeted lipidomics can be used as a qualitative method to rapidly assess the toxicity of aminoglycosides in HeLa and primary cells. Moreover, these results demonstrate there is no direct correlation between the ratio of cardiolipins to phosphatidylinositols and the maximal mitochondrial respiratory capacity.
Publication Date: 20-Aug-2018
Date of Acceptance: 27-Jun-2018
URI: http://hdl.handle.net/10044/1/61862
DOI: https://dx.doi.org/10.1021/acs.chemrestox.8b00038
ISSN: 0893-228X
Publisher: American Chemical Society
Start Page: 688
End Page: 696
Journal / Book Title: Chemical Research in Toxicology
Volume: 31
Issue: 8
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/M027007/1
EP/M027007/1
Copyright Statement: © 2018 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Keywords: 0302 Inorganic Chemistry
0304 Medicinal And Biomolecular Chemistry
0305 Organic Chemistry
Toxicology
Publication Status: Published
Online Publication Date: 2018-06-27
Appears in Collections:Department of Medicine
Faculty of Natural Sciences



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