The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux

Julia Vergalli (1) , Alessio Atzori (2) , Jelena Pajovic (3) , Estelle Dumont (1) , Giuliano Malloci (2) , Muriel Masi (1, 4) , Attilio Vittorio Vargiu (2) , Mathias Winterhalter (5) , Matthieu Réfrégiers (6) , Paolo Ruggerone (2) , Jean-Marie Pagès (1)

1 MCT - Membranes et cibles thérapeutiques
2 UniCa - Università degli Studi di Cagliari = University of Cagliari
3 University of Belgrade [Belgrade]
4 Université Paris-Saclay
5 Jacobs University = Constructor University [Bremen]
6 SSOLEIL - Synchrotron SOLEIL

With the spreading of antibiotic resistance, the translocation of antibiotics through bacterial envelopes is crucial for their antibacterial activity. In Gram-negative bacteria, the interplay between membrane permeability and drug efflux pumps must be investigated as a whole. Here, we quantified the intracellular accumulation of a series of fluoroquinolones in population and in individual cells of Escherichia coli according to the expression of the AcrB efflux transporter. Computational results supported the accumulation levels measured experimentally and highlighted how fluoroquinolones side chains interact with specific residues of the distal pocket of the AcrB tight monomer during recognition and binding steps.

Mots clés: Antimicrobial resistance; Molecular modelling

Domaines: Sciences du Vivant [q-bio]; Sciences de l'environnement

Julia Vergalli, Alessio Atzori, Jelena Pajovic, Estelle Dumont, Giuliano Malloci, et al.. The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux. Communications Biology, 2020, 3 (1), ⟨10.1038/s42003-020-0929-x⟩. ⟨hal-03220501⟩