Thesis
The Perks of Stress: Characterizing the Role of the PERK-eIF2[alpha] Pathway in Tick-Pathogen Interactions
Washington State University
Master of Science (MS), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000003335
Handle:
https://hdl.handle.net/2376/122283
Abstract
The North American deer tick, Ixodes scapularis, is a medically important arthropod that can transmit up to seven different pathogens, including Borrelia burgdorferi (Lyme disease) and Anaplasma phagocytophilum (human granulocytic anaplasmosis). Yet, it is unclear why I. scapularis can transmit such a wide range of pathogens. Vector competence, a vector’s ability to acquire, maintain, and transmit pathogens, is influenced by a variety of factors, including the arthropod innate immune system. Identifying factors that disrupt tick-pathogen interactions can aid in reducing pathogen transmission to human and animal hosts. In mammals, stress response pathways are closely intertwined with immune signaling. Whether stress response pathways influence vector competence of ticks is unknown. Stress granules (SGs), a stress response mechanism, may potentially interfere with tick-pathogen interactions. During cellular stress, a stress-sensing kinase, such as PERK (PKR-like endoplasmic reticulum kinase) phosphorylates eIF2α and causes SG formation. SGs can act as an antimicrobial defense mechanism that prevents viral replication or can become signaling hubs that sequester molecules to modulate immune responses. We hypothesized that the PERK-eIF2α signaling pathway influences vector competence of I. scapularis through the production of SGs. In this study, we showed that the PERK-eIF2α signaling pathway, a branch of the integrated stress response, is activated during B. burgdorferi and A. phagocytophilum infection. By silencing perk and eif2α expression in vitro and in vivo, we demonstrated that the PERK-eIF2α signaling pathway is beneficial for bacterial colonization. We also knocked down SG genes (pabp1, g3bp1, and tia1) important for SG formation, and found that tia1 significantly reduced bacterial load in vitro, whereas g3bp1 and pabp1 promoted colonization. These data indicates that TIA1 is benefiting bacterial colonization, however it is unclear if it is through SG formation. Altogether, our data suggests that the PERK-eIF2α pathway influences I. scapularis acquisition of tick-borne pathogens. This is evidence that stress response mechanisms impact vector competence of ticks.
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Details
- Title
- The Perks of Stress
- Creators
- Joanna Hurtado
- Contributors
- Dana Kathleen Shaw (Chair) - Washington State University, Department of Veterinary Microbiology and PathologyAlan G Goodman (Committee Member) - Washington State University, School of Molecular BiosciencesAnthony Nicola (Committee Member) - Washington State University, Department of Veterinary Microbiology and PathologyJennifer L Watts (Committee Member) - Washington State University, School of Molecular Biosciences
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 45
- Identifiers
- 99900652102101842
- Language
- English
- Resource Type
- Thesis