Fluoroquinolone structure and translocation flux across bacterial membrane

Julia Vergalli (1) , Estelle Dumont (1) , Bertrand Cinquin (2) , Laure Maigre (1) , Jelena Pajovic (2, 3) , Eric Bacqué (4) , Michael Mourez (4) , Matthieu M. Refregiers (2) , Jean-Marie Pagès (1)

1 TMCD2 - Transporteurs membranaires, chimioresistance et drug-design
2 SSOLEIL - Synchrotron SOLEIL
3 University of Belgrade [Belgrade]
4 SANOFI Recherche

Bacterial multidrug resistance is a worrying health issue. In Gram-negative antibacterial research, the challenge is to define the antibiotic permeation across the membranes. Passing through the membrane barrier to reach the inhibitory concentration inside the bacterium is a pivotal step for antibacterial molecules. A spectrofluorimetric methodology has been developed to detect fluoroquinolones in bacterial population and inside individual Gram-negative bacterial cells. In this work, we studied the antibiotic accumulation in cells expressing various levels of efflux pumps. The assays allow us to determine the intracellular concentration of the fluoroquinolones to study the relationships between the level of efflux activity and the antibiotic accumulation, and finally to evaluate the impact of fluoroquinolone structures in this process. This represents the first protocol to identify some structural parameters involved in antibiotic translocation and accumulation, and to illustrate the recently proposed " Structure Intracellular Concentration Activity Relationship " (SICAR) concept.

Domaines: Biophysique; Bactériologie; Sciences pharmaceutiques

Julia Vergalli, Estelle Dumont, Bertrand Cinquin, Laure Maigre, Jelena Pajovic, et al.. Fluoroquinolone structure and translocation flux across bacterial membrane. Scientific Reports, 2017, 7 (1), pp.9821 ⟨10.1038/s41598-017-08775-4⟩. ⟨hal-01582320⟩