Fluoroquinolone Structure and Translocation Flux Across Bacterial Membrane

Overview

Journal Sci Rep

Specialty Science

Date 2017 Aug 31

PMID 28851902

Citations 26

Authors

Julia Vergalli

Estelle Dumont

Bertrand Cinquin

Laure Maigre

Jelena Pajovic

Eric Bacque

Michael Mourez

Matthieu Refregiers

Jean-Marie Pages

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Intracellular Quantification of an Antibiotic Metal Complex in Single Cells of Using Cryo-X-ray Fluorescence Nanoimaging.

Draveny M, Chauvet H, Rouam V, Jamme F, Masi M ACS Nano. 2024; 19(1):979-988.

PMID: 39740123 PMC: 11771837. DOI: 10.1021/acsnano.4c12664.

Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane.

Vergalli J, Refregiers M, Ruggerone P, Winterhalter M, Pages J Commun Biol. 2024; 7(1):1508.

PMID: 39543341 PMC: 11564671. DOI: 10.1038/s42003-024-07168-4.

Budmunchiamines as a Potential Adjuvant for Rejuvenating Phenicol Activities towards -Resistant Strains.

Dofini Magnini R, Pedinielli F, Vergalli J, Ouedraogo N, Remy S, Hilou A Int J Mol Sci. 2023; 24(10).

PMID: 37240134 PMC: 10218413. DOI: 10.3390/ijms24108790.

Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives.

Tabcheh J, Vergalli J, Davin-Regli A, Ghanem N, Pages J, Al-Bayssari C Int J Mol Sci. 2023; 24(2).

PMID: 36675027 PMC: 9864949. DOI: 10.3390/ijms24021515.

A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones.

Vergalli J, Chauvet H, Oliva F, Pajovic J, Malloci G, Vargiu A Commun Biol. 2022; 5(1):1062.

PMID: 36203030 PMC: 9537517. DOI: 10.1038/s42003-022-04024-1.

References

Bolla J, Alibert-Franco S, Handzlik J, Chevalier J, Mahamoud A, Boyer G . Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria. FEBS Lett. 2011; 585(11):1682-90. DOI: 10.1016/j.febslet.2011.04.054. View

Pages J, James C, Winterhalter M . The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008; 6(12):893-903. DOI: 10.1038/nrmicro1994. View

Stavenger R, Winterhalter M . TRANSLOCATION project: how to get good drugs into bad bugs. Sci Transl Med. 2014; 6(228):228ed7. DOI: 10.1126/scitranslmed.3008605. View

Masi M, Refregiers M, Pos K, Pages J . Mechanisms of envelope permeability and antibiotic influx and efflux in Gram-negative bacteria. Nat Microbiol. 2017; 2:17001. DOI: 10.1038/nmicrobiol.2017.1. View

Misra R, Morrison K, Cho H, Khuu T . Importance of Real-Time Assays To Distinguish Multidrug Efflux Pump-Inhibiting and Outer Membrane-Destabilizing Activities in Escherichia coli. J Bacteriol. 2015; 197(15):2479-88. PMC: 4518837. DOI: 10.1128/JB.02456-14. View

Vardakas K, Falagas M . Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. Int J Antimicrob Agents. 2016; 49(2):233-238. DOI: 10.1016/j.ijantimicag.2016.07.023. View

Kollef M, Bassetti M, Francois B, Burnham J, Dimopoulos G, Garnacho-Montero J . The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship. Intensive Care Med. 2017; 43(9):1187-1197. PMC: 6204331. DOI: 10.1007/s00134-017-4682-7. View

Nikaido H . Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994; 264(5157):382-8. DOI: 10.1126/science.8153625. View

Jamme F, Villette S, Giuliani A, Rouam V, Wien F, Lagarde B . Synchrotron UV fluorescence microscopy uncovers new probes in cells and tissues. Microsc Microanal. 2010; 16(5):507-14. DOI: 10.1017/S1431927610093852. View

10.

Davis T, Gerry C, Tan D . General platform for systematic quantitative evaluation of small-molecule permeability in bacteria. ACS Chem Biol. 2014; 9(11):2535-44. PMC: 4245172. DOI: 10.1021/cb5003015. View

11.

Blair J, Piddock L . How to Measure Export via Bacterial Multidrug Resistance Efflux Pumps. mBio. 2016; 7(4). PMC: 4958252. DOI: 10.1128/mBio.00840-16. View

12.

Davin-Regli A, Bolla J, James C, Lavigne J, Chevalier J, Garnotel E . Membrane permeability and regulation of drug "influx and efflux" in enterobacterial pathogens. Curr Drug Targets. 2008; 9(9):750-9. DOI: 10.2174/138945008785747824. View

13.

Cinquin B, Maigre L, Pinet E, Chevalier J, Stavenger R, Mills S . Microspectrometric insights on the uptake of antibiotics at the single bacterial cell level. Sci Rep. 2015; 5:17968. PMC: 4675965. DOI: 10.1038/srep17968. View

14.

Blair J, Webber M, Baylay A, Ogbolu D, Piddock L . Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2014; 13(1):42-51. DOI: 10.1038/nrmicro3380. View

15.

Mamelli L, Petit S, Chevalier J, Giglione C, Lieutaud A, Meinnel T . New antibiotic molecules: bypassing the membrane barrier of gram negative bacteria increases the activity of peptide deformylase inhibitors. PLoS One. 2009; 4(7):e6443. PMC: 2713832. DOI: 10.1371/journal.pone.0006443. View

16.

Zhou Y, Joubran C, Miller-Vedam L, Isabella V, Nayar A, Tentarelli S . Thinking outside the "bug": a unique assay to measure intracellular drug penetration in gram-negative bacteria. Anal Chem. 2015; 87(7):3579-84. DOI: 10.1021/ac504880r. View

17.

Carey P, Heidari-Torkabadi H . New techniques in antibiotic discovery and resistance: Raman spectroscopy. Ann N Y Acad Sci. 2015; 1354:67-81. DOI: 10.1111/nyas.12847. View

18.

Phetsang W, Pelingon R, Butler M, Kc S, Pitt M, Kaeslin G . Fluorescent Trimethoprim Conjugate Probes To Assess Drug Accumulation in Wild Type and Mutant Escherichia coli. ACS Infect Dis. 2016; 2(10):688-701. PMC: 5067704. DOI: 10.1021/acsinfecdis.6b00080. View

19.

Nikaido H . Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003; 67(4):593-656. PMC: 309051. DOI: 10.1128/MMBR.67.4.593-656.2003. View

20.

Edelstein A, Amodaj N, Hoover K, Vale R, Stuurman N . Computer control of microscopes using µManager. Curr Protoc Mol Biol. 2010; Chapter 14:Unit14.20. PMC: 3065365. DOI: 10.1002/0471142727.mb1420s92. View