An obligate intracellular bacterial pathogen forms extensive and stable interkingdom contacts with the endoplasmic reticulum
Name
AcevedoSanchez-yacevedo-PhD-Biology-2024-thesis.pdf
Description
Thesis PDF
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18.33 MB
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29a905801e24644f6bc0f8675355874b
Author(s)
Acevedo-Sánchez, Yamilex
Advisor(s)
Lamason, Rebecca L.
Date Issued
May 2024
Publisher
Massachusetts Institute of Technology
Abstract
Intracellular pathogens employ various mechanisms to manipulate host membranes, a critical strategy for subverting host pathways and advancing their life cycle. To this end, Rickettsia parkeri directly engages the host plasma membrane to infiltrate target cells and spread to neighboring ones. However, whether this pathogen directly engages other cellular membranes during infection remains unclear. Interestingly, a report showed a single example of rough ER membranes encircling a rickettsial isolate, reminiscent of membrane contact sites (MCSs), where organelle membranes closely interact. MCSs play pivotal roles in maintaining cellular homeostasis and facilitating communication and trafficking within the cell. While vacuolar bacterial pathogens and viruses are known to exploit MCSs, the formation of these sites by cytosolic pathogens has not been extensively investigated. In my research, I demonstrate that R. parkeri interacts with the rough ER. Moreover, I show that this interaction has membrane contact site-like properties. These contacts are stable and extensive and are regulated by VAP proteins. Thus, I propose that R. parkeri forms a direct interkingdom MCS with the ER. Even though the functional implications of this interaction remain unknown at the culmination of my thesis, my findings offer a more nuanced understanding of the cellular landscape during R. parkeri infection, showing that this pathogen engages additional cellular membranes beyond the host plasma membrane. Furthermore, this discovery highlights the importance of studying neglected pathogens like R. parkeri and utilizing them as valuable tools for discovering new aspects of biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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