Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i>
The tripartite complex AcrAB-TolC is the major RND pump in <i>Escherichia coli</i> and other Enterobacteriaceae, including <i>Shigella</i>, the etiological agent of bacillary dysentery. In addition to conferring resistance to many classes of antibiotics, AcrAB plays a role in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/5/823 |
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| author | Marco Coluccia Aude Béranger Rita Trirocco Giulia Fanelli Francesco Zanzi Bianca Colonna Milena Grossi Gianni Prosseda Martina Pasqua |
| author_facet | Marco Coluccia Aude Béranger Rita Trirocco Giulia Fanelli Francesco Zanzi Bianca Colonna Milena Grossi Gianni Prosseda Martina Pasqua |
| author_sort | Marco Coluccia |
| collection | DOAJ |
| description | The tripartite complex AcrAB-TolC is the major RND pump in <i>Escherichia coli</i> and other Enterobacteriaceae, including <i>Shigella</i>, 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 <i>Shigella flexneri</i> invasion of epithelial cells. We found that deletion of both <i>acrA</i> and <i>acrB</i> genes causes reduced survival of <i>S. flexneri</i> 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 <i>Shigella</i>, and add insights into the mechanism governing the <i>Shigella</i> infection process. |
| first_indexed | 2024-03-11T03:54:26Z |
| format | Article |
| id | doaj.art-165bdc0576d84c7299d254434316008b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T03:54:26Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-165bdc0576d84c7299d254434316008b2023-11-18T00:39:43ZengMDPI AGBiomolecules2218-273X2023-05-0113582310.3390/biom13050823Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i>Marco Coluccia0Aude Béranger1Rita Trirocco2Giulia Fanelli3Francesco Zanzi4Bianca Colonna5Milena Grossi6Gianni Prosseda7Martina Pasqua8Istituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyIstituto Pasteur Italy, Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome, 00185 Rome, ItalyThe tripartite complex AcrAB-TolC is the major RND pump in <i>Escherichia coli</i> and other Enterobacteriaceae, including <i>Shigella</i>, 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 <i>Shigella flexneri</i> invasion of epithelial cells. We found that deletion of both <i>acrA</i> and <i>acrB</i> genes causes reduced survival of <i>S. flexneri</i> 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 <i>Shigella</i>, and add insights into the mechanism governing the <i>Shigella</i> infection process.https://www.mdpi.com/2218-273X/13/5/823<i>Shigella</i>AcrABefflux pumpsmicrobe–host cell interaction |
| spellingShingle | Marco Coluccia Aude Béranger Rita Trirocco Giulia Fanelli Francesco Zanzi Bianca Colonna Milena Grossi Gianni Prosseda Martina Pasqua Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> Biomolecules <i>Shigella</i> AcrAB efflux pumps microbe–host cell interaction |
| title | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> |
| title_full | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> |
| title_fullStr | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> |
| title_full_unstemmed | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> |
| title_short | Role of the MDR Efflux Pump AcrAB in Epithelial Cell Invasion by <i>Shigella flexneri</i> |
| title_sort | role of the mdr efflux pump acrab in epithelial cell invasion by i shigella flexneri i |
| topic | <i>Shigella</i> AcrAB efflux pumps microbe–host cell interaction |
| url | https://www.mdpi.com/2218-273X/13/5/823 |
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