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.

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

Atzori A.;Malloci G.;Vargiu A. V.;Winterhalter M.;Ruggerone P.;
2020-01-01

Abstract

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.
2020
fluoroquinolones; accumulation; bacterial efflux systems; molecular modeling; molecular dynamics
File in questo prodotto:
File Dimensione Formato  
s42003-020-0929-x.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: versione editoriale
Dimensione 1.67 MB
Formato Adobe PDF
1.67 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/291538
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 31
social impact