Upon invasion into the host cell, a subset of bacterial pathogens resides exclusively in the cytosol. While previous research revealed how they reshape the plasma membrane during invasion, subvert the immune response, and hijack cytoskeletal dynamics to promote their motility, it was unclear if these pathogens also interacted with the organelles in this crowded intracellular space. Here, we examined if the obligate intracellular pathogen Rickettsia parkeri interacts with the endoplasmic reticulum (ER), a large and dynamic organelle spread throughout the cell. Using live-cell microscopy and transmission and focused-ion-beam scanning electron microscopy, we show that R. parkeri forms extensive contacts with the rough ER that are ∼55 nm apart and cover more than half the bacterial surface. Depletion of the ER-specific tethers VAPA and VAPB reduced rickettsia–ER contacts, and VAPA and VAPB were localized around intracellular rickettsiae. Overall, our findings illuminate an interkingdom ER contact uniquely mediated by rickettsiae that mimics some characteristics of traditional host membrane contact sites.
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January 07 2025
Rickettsia parkeri forms extensive, stable contacts with the rough endoplasmic reticulum
Yamilex Acevedo-Sánchez
,
Yamilex Acevedo-Sánchez
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
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Patrick J. Woida
,
Patrick J. Woida
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
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Caroline Anderson
,
Caroline Anderson
(Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - review & editing)
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
2
Microbiology Program, Massachusetts Institute of Technology
, Cambridge, MA, USA
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Stephan Kraemer
,
Stephan Kraemer
(Data curation, Formal analysis, Methodology, Resources, Software, Writing - review & editing)
3
Center for Nanoscale Systems, Harvard University
, Cambridge, MA, USA
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Rebecca L. Lamason
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
2
Microbiology Program, Massachusetts Institute of Technology
, Cambridge, MA, USA
Correspondence to Rebecca L. Lamason: [email protected]
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Yamilex Acevedo-Sánchez
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
Patrick J. Woida
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - original draft, Writing - review & editing
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
Caroline Anderson
Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - review & editing
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
2
Microbiology Program, Massachusetts Institute of Technology
, Cambridge, MA, USA
Stephan Kraemer
Data curation, Formal analysis, Methodology, Resources, Software, Writing - review & editing
3
Center for Nanoscale Systems, Harvard University
, Cambridge, MA, USA
Rebecca L. Lamason
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Biology,
Massachusetts Institute of Technology
, Cambridge, MA, USA
2
Microbiology Program, Massachusetts Institute of Technology
, Cambridge, MA, USA
Correspondence to Rebecca L. Lamason: [email protected]
Disclosures: The authors declare no competing interests exist.
Received:
June 21 2024
Revision Received:
November 25 2024
Accepted:
December 10 2024
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funder(s):
National Science Foundation
- Award Id(s): ECCS-2025158
Funder(s):
National Institutes of Health
- Award Id(s): T32GM007287,R01GM141025,R01AI155489
© 2025 Acevedo-Sánchez et al.
2024
Acevedo-Sanchez et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (3): e202406122.
Article history
Received:
June 21 2024
Revision Received:
November 25 2024
Accepted:
December 10 2024
Citation
Yamilex Acevedo-Sánchez, Patrick J. Woida, Caroline Anderson, Stephan Kraemer, Rebecca L. Lamason; Rickettsia parkeri forms extensive, stable contacts with the rough endoplasmic reticulum. J Cell Biol 3 March 2025; 224 (3): e202406122. doi: https://doi.org/10.1083/jcb.202406122
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