Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry
Summary: The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using in...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723014067 |
| _version_ | 1797448064105971712 |
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| author | Fan Yang Mingyi Suo Homayemem Weli Mason Wong Alex Junidi Celeste Cummings Ryan Johnson Kiara Mallory Annie Y. Liu Zev J. Greenberg Laura G. Schuettpelz Mark J. Miller Cliff J. Luke Gwendalyn J. Randolph Bernd H. Zinselmeyer Juliane Bubeck Wardenburg Regina A. Clemens |
| author_facet | Fan Yang Mingyi Suo Homayemem Weli Mason Wong Alex Junidi Celeste Cummings Ryan Johnson Kiara Mallory Annie Y. Liu Zev J. Greenberg Laura G. Schuettpelz Mark J. Miller Cliff J. Luke Gwendalyn J. Randolph Bernd H. Zinselmeyer Juliane Bubeck Wardenburg Regina A. Clemens |
| author_sort | Fan Yang |
| collection | DOAJ |
| description | Summary: The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla suppressed calcium signaling in vitro and in vivo and calcium-dependent leukotriene B4 (LTB4) production, a key mediator of neutrophil clustering. Thus, Hla disrupts the early patterning of the neutrophil response to infection, in part through direct impairment of neutrophil calcium signaling. This early mis-localization of neutrophils may contribute to establishment of infection. |
| first_indexed | 2024-03-09T14:04:58Z |
| format | Article |
| id | doaj.art-8ce12c2e775c4ee4b7824ce089eedc43 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-09T14:04:58Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8ce12c2e775c4ee4b7824ce089eedc432023-11-30T05:07:03ZengElsevierCell Reports2211-12472023-11-014211113394Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entryFan Yang0Mingyi Suo1Homayemem Weli2Mason Wong3Alex Junidi4Celeste Cummings5Ryan Johnson6Kiara Mallory7Annie Y. Liu8Zev J. Greenberg9Laura G. Schuettpelz10Mark J. Miller11Cliff J. Luke12Gwendalyn J. Randolph13Bernd H. Zinselmeyer14Juliane Bubeck Wardenburg15Regina A. Clemens16Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding authorSummary: The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla suppressed calcium signaling in vitro and in vivo and calcium-dependent leukotriene B4 (LTB4) production, a key mediator of neutrophil clustering. Thus, Hla disrupts the early patterning of the neutrophil response to infection, in part through direct impairment of neutrophil calcium signaling. This early mis-localization of neutrophils may contribute to establishment of infection.http://www.sciencedirect.com/science/article/pii/S2211124723014067CP: MicrobiologyCP: Cell biology |
| spellingShingle | Fan Yang Mingyi Suo Homayemem Weli Mason Wong Alex Junidi Celeste Cummings Ryan Johnson Kiara Mallory Annie Y. Liu Zev J. Greenberg Laura G. Schuettpelz Mark J. Miller Cliff J. Luke Gwendalyn J. Randolph Bernd H. Zinselmeyer Juliane Bubeck Wardenburg Regina A. Clemens Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry Cell Reports CP: Microbiology CP: Cell biology |
| title | Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry |
| title_full | Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry |
| title_fullStr | Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry |
| title_full_unstemmed | Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry |
| title_short | Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry |
| title_sort | staphylococcus aureus α toxin impairs early neutrophil localization via electrogenic disruption of store operated calcium entry |
| topic | CP: Microbiology CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723014067 |
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