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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<jats:italic>Escherichia coli<\/jats:italic>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.<\/jats:p>","DOI":"10.1038\/s42003-020-0929-x","type":"journal-article","created":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T10:04:21Z","timestamp":1588068261000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["The challenge of intracellular antibiotic accumulation, a function of fluoroquinolone influx versus bacterial efflux"],"prefix":"10.1038","volume":"3","author":[{"given":"Julia","family":"Vergalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Atzori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Pajovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Dumont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-257X","authenticated-orcid":false,"given":"Giuliano","family":"Malloci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-8867","authenticated-orcid":false,"given":"Attilio Vittorio","family":"Vargiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-3318","authenticated-orcid":false,"given":"Mathias","family":"Winterhalter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-2308","authenticated-orcid":false,"given":"Matthieu","family":"R\u00e9fr\u00e9giers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-0824","authenticated-orcid":false,"given":"Paolo","family":"Ruggerone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-7977","authenticated-orcid":false,"given":"Jean-Marie","family":"Pag\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"929_CR1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/nrd3289","volume":"9","author":"D Jones","year":"2010","unstructured":"Jones, D. 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