{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:02:23Z","timestamp":1788350543142,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006601","name":"Italian Ministry of Foreign Affairs and International Cooperation","doi-asserted-by":"publisher","award":["JP21GR04"],"award-info":[{"award-number":["JP21GR04"]}],"id":[{"id":"10.13039\/501100006601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006601","name":"Italian Ministry of Foreign Affairs and International Cooperation","doi-asserted-by":"publisher","award":["AR2221816BAF1B0B"],"award-info":[{"award-number":["AR2221816BAF1B0B"]}],"id":[{"id":"10.13039\/501100006601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["JP21GR04"],"award-info":[{"award-number":["JP21GR04"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["AR2221816BAF1B0B"],"award-info":[{"award-number":["AR2221816BAF1B0B"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The tripartite complex AcrAB-TolC is the major RND pump in Escherichia coli and other Enterobacteriaceae, including Shigella, the etiological agent of bacillary dysentery. In addition to conferring resistance to many classes of antibiotics, AcrAB plays a role in the pathogenesis and virulence of several bacterial pathogens. Here, we report data demonstrating that AcrAB specifically contributes to Shigella flexneri invasion of epithelial cells. We found that deletion of both acrA and acrB genes causes reduced survival of S. flexneri M90T strain within Caco-2 epithelial cells and prevents cell-to-cell spread of the bacteria. Infections with single deletion mutant strains indicate that both AcrA and AcrB favor the viability of the intracellular bacteria. Finally, we were able to further confirm the requirement of the AcrB transporter activity for intraepithelial survival by using a specific EP inhibitor. Overall, the data from the present study expand the role of the AcrAB pump to an important human pathogen, such as Shigella, and add insights into the mechanism governing the Shigella infection process.<\/jats:p>","DOI":"10.3390\/biom13050823","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T02:36:59Z","timestamp":1683859019000},"page":"823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri"],"prefix":"10.3390","volume":"13","author":[{"given":"Marco","family":"Coluccia","sequence":"first","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"B\u00e9ranger","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Trirocco","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8187-9747","authenticated-orcid":false,"given":"Francesco","family":"Zanzi","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Colonna","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-9189","authenticated-orcid":false,"given":"Milena","family":"Grossi","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-0086","authenticated-orcid":false,"given":"Gianni","family":"Prosseda","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Pasqua","sequence":"additional","affiliation":[{"name":"Istituto Pasteur Italy, Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin. 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