The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate
ABSTRACT Intestinal epithelial cells represent the first line of defense from invading enteric pathogens. During the course of infection, pro-inflammatory programmed cell death is an effective way to eliminate invading microbes and to create a localized inflammatory environment. On the other hand, p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00775-23 |
| _version_ | 1827586757063868416 |
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| author | Lisa Perruzza Carlo Zagaglia Laura Vitiello Meysam Sarshar Francesco Strati Martina Pasqua Fabio Grassi Mauro Nicoletti Anna Teresa Palamara Cecilia Ambrosi Daniela Scribano |
| author_facet | Lisa Perruzza Carlo Zagaglia Laura Vitiello Meysam Sarshar Francesco Strati Martina Pasqua Fabio Grassi Mauro Nicoletti Anna Teresa Palamara Cecilia Ambrosi Daniela Scribano |
| author_sort | Lisa Perruzza |
| collection | DOAJ |
| description | ABSTRACT Intestinal epithelial cells represent the first line of defense from invading enteric pathogens. During the course of infection, pro-inflammatory programmed cell death is an effective way to eliminate invading microbes and to create a localized inflammatory environment. On the other hand, pathogens evolved countless strategies to overcome cell death and to keep the host alive ensuring their spread. It was previously shown that Shigella flexneri apyrase interacts with OmpA to contribute to a proper polar exposition of IcsA, which mediates actin-based motility. However, apyrase is also an ATP-diphosphohydrolase whose catalytic activity function has not been elucidated yet. Herein, we demonstrated that apyrase contributes to the manipulation of host cell fate by S. flexneri since it is released within the host cell cytoplasm during infection to degrade intracellular ATP. Thus, apyrase contributes to prevent caspase-1 activation, thereby downregulating the activation of pyroptosis in infected cells. Overall, apyrase is involved in the modulation of host cell survival and dampens the inflammatory response. IMPORTANCE In this paper, we demonstrated that apyrase is released within the host cell cytoplasm during infection to target the intracellular ATP pool. By degrading intracellular ATP, apyrase contributes to prevent caspases activation, thereby inhibiting the activation of pyroptosis in infected cells. Our results show, for the first time, that apyrase is involved in the modulation of host cell survival, thereby aiding this pathogen to dampen the inflammatory response. This work adds a further piece to the puzzle of Shigella pathogenesis. Due to its increased spread worldwide, prevention and controlling strategies are urgently needed. Overall, this study highlighted apyrase as a suitable target for an anti-virulence therapy to tackle this pathogen. |
| first_indexed | 2024-03-09T00:06:19Z |
| format | Article |
| id | doaj.art-7ccb2819d8c0495d9af1bb1fce3b45dc |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:19Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-7ccb2819d8c0495d9af1bb1fce3b45dc2023-12-12T13:17:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.00775-23The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fateLisa Perruzza0Carlo Zagaglia1Laura Vitiello2Meysam Sarshar3Francesco Strati4Martina Pasqua5Fabio Grassi6Mauro Nicoletti7Anna Teresa Palamara8Cecilia Ambrosi9Daniela Scribano10Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana , Bellinzona, SwitzerlandDepartment of Public Health and Infectious Diseases, Sapienza University of Rome , Rome, ItalyLaboratory of Flow Cytometry, IRCCS San Raffaele Roma , Rome, ItalyResearch Laboratories, Bambino Gesù Children’s Hospital, IRCCS , Rome, ItalyMucosal Immunology Lab, Department of Biotechnology and Biosciences, University of Milano-Bicocca , Milan, ItalyInstitute Pasteur Italy, Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome , Rome, ItalyInstitute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana , Bellinzona, SwitzerlandDepartment of Public Health and Infectious Diseases, Sapienza University of Rome , Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory Affiliated to Institute Pasteur Italia-Cenci Bolognetti Foundation , Rome, ItalyDepartment of Human Sciences and Quality of Life Promotion, San Raffaele University , Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome , Rome, ItalyABSTRACT Intestinal epithelial cells represent the first line of defense from invading enteric pathogens. During the course of infection, pro-inflammatory programmed cell death is an effective way to eliminate invading microbes and to create a localized inflammatory environment. On the other hand, pathogens evolved countless strategies to overcome cell death and to keep the host alive ensuring their spread. It was previously shown that Shigella flexneri apyrase interacts with OmpA to contribute to a proper polar exposition of IcsA, which mediates actin-based motility. However, apyrase is also an ATP-diphosphohydrolase whose catalytic activity function has not been elucidated yet. Herein, we demonstrated that apyrase contributes to the manipulation of host cell fate by S. flexneri since it is released within the host cell cytoplasm during infection to degrade intracellular ATP. Thus, apyrase contributes to prevent caspase-1 activation, thereby downregulating the activation of pyroptosis in infected cells. Overall, apyrase is involved in the modulation of host cell survival and dampens the inflammatory response. IMPORTANCE In this paper, we demonstrated that apyrase is released within the host cell cytoplasm during infection to target the intracellular ATP pool. By degrading intracellular ATP, apyrase contributes to prevent caspases activation, thereby inhibiting the activation of pyroptosis in infected cells. Our results show, for the first time, that apyrase is involved in the modulation of host cell survival, thereby aiding this pathogen to dampen the inflammatory response. This work adds a further piece to the puzzle of Shigella pathogenesis. Due to its increased spread worldwide, prevention and controlling strategies are urgently needed. Overall, this study highlighted apyrase as a suitable target for an anti-virulence therapy to tackle this pathogen.https://journals.asm.org/doi/10.1128/spectrum.00775-23Shigella flexneriapyraseATPpyroptosisinflammationhost cell survival |
| spellingShingle | Lisa Perruzza Carlo Zagaglia Laura Vitiello Meysam Sarshar Francesco Strati Martina Pasqua Fabio Grassi Mauro Nicoletti Anna Teresa Palamara Cecilia Ambrosi Daniela Scribano The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate Microbiology Spectrum Shigella flexneri apyrase ATP pyroptosis inflammation host cell survival |
| title | The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| title_full | The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| title_fullStr | The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| title_full_unstemmed | The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| title_short | The Shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| title_sort | shigella flexneri virulence factor apyrase is released inside eukaryotic cells to hijack host cell fate |
| topic | Shigella flexneri apyrase ATP pyroptosis inflammation host cell survival |
| url | https://journals.asm.org/doi/10.1128/spectrum.00775-23 |
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