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Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri
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 sev...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216353/ https://www.ncbi.nlm.nih.gov/pubmed/37238693 http://dx.doi.org/10.3390/biom13050823 |
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author | Coluccia, Marco Béranger, Aude Trirocco, Rita Fanelli, Giulia Zanzi, Francesco Colonna, Bianca Grossi, Milena Prosseda, Gianni Pasqua, Martina |
author_facet | Coluccia, Marco Béranger, Aude Trirocco, Rita Fanelli, Giulia Zanzi, Francesco Colonna, Bianca Grossi, Milena Prosseda, Gianni Pasqua, Martina |
author_sort | Coluccia, Marco |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10216353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102163532023-05-27 Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri Coluccia, Marco Béranger, Aude Trirocco, Rita Fanelli, Giulia Zanzi, Francesco Colonna, Bianca Grossi, Milena Prosseda, Gianni Pasqua, Martina Biomolecules Article 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. MDPI 2023-05-11 /pmc/articles/PMC10216353/ /pubmed/37238693 http://dx.doi.org/10.3390/biom13050823 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Coluccia, Marco Béranger, Aude Trirocco, Rita Fanelli, Giulia Zanzi, Francesco Colonna, Bianca Grossi, Milena Prosseda, Gianni Pasqua, Martina Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title_full | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title_fullStr | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title_full_unstemmed | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title_short | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by Shigella flexneri |
title_sort | role of the mdr efflux pump acrab in epithelial cell invasion by shigella flexneri |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216353/ https://www.ncbi.nlm.nih.gov/pubmed/37238693 http://dx.doi.org/10.3390/biom13050823 |
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