دورية أكاديمية
The role of Rab27 in tick extracellular vesicle biogenesis and pathogen infection.
العنوان: | The role of Rab27 in tick extracellular vesicle biogenesis and pathogen infection. |
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المؤلفون: | Butler LR; The University of Maryland Baltimore, Baltimore, MD, USA.; Harvard Medical School, Boston, MA, USA., Singh N; The University of Maryland Baltimore, Baltimore, MD, USA., Marnin L; The University of Maryland Baltimore, Baltimore, MD, USA., Valencia LM; The University of Maryland Baltimore, Baltimore, MD, USA., O'Neal AJ; The University of Maryland Baltimore, Baltimore, MD, USA.; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Paz FEC; The University of Maryland Baltimore, Baltimore, MD, USA., Shaw DK; Washington State University, Pullman, WA, USA., Chavez ASO; Texas A&M University, College Station, TX, USA., Pedra JHF; The University of Maryland Baltimore, Baltimore, MD, USA. jpedra@som.umaryland.edu. |
المصدر: | Parasites & vectors [Parasit Vectors] 2024 Feb 09; Vol. 17 (1), pp. 57. Date of Electronic Publication: 2024 Feb 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101462774 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-3305 (Electronic) Linking ISSN: 17563305 NLM ISO Abbreviation: Parasit Vectors Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central |
مواضيع طبية MeSH: | Anaplasma phagocytophilum*/physiology , Ixodes*/cytology , Ixodes*/metabolism , Ixodes*/microbiology , Extracellular Vesicles*/metabolism , rab27 GTP-Binding Proteins*/metabolism , Arthropod Proteins*/metabolism, Animals ; Humans ; Mice ; Mammals |
مستخلص: | Background: The blacklegged tick, Ixodes scapularis, transmits most vector-borne diseases in the US. It vectors seven pathogens of public health relevance, including the emerging human pathogen Anaplasma phagocytophilum. Nevertheless, it remains critically understudied compared to other arthropod vectors. Ixodes scapularis releases a variety of molecules that assist in the modulation of host responses. Recently, it was found that extracellular vesicles (EVs) carry several of these molecules and may impact microbial transmission to the mammalian host. EV biogenesis has been studied in mammalian systems and is relatively well understood, but the molecular players important for the formation and secretion of EVs in arthropods of public health relevance remain elusive. RabGTPases are among the major molecular players in mammalian EV biogenesis. They influence membrane identity and vesicle budding, uncoating, and motility. Methods: Using BLAST, an in silico pathway for EV biogenesis in ticks was re-constructed. We identified Rab27 for further study. EVs were collected from ISE6 tick cells after knocking down rab27 to examine its role in tick EV biogenesis. Ixodes scapularis nymphs were injected with small interfering RNAs to knock down rab27 and then fed on naïve and A. phagocytophilum-infected mice to explore the importance of rab27 in tick feeding and bacterial acquisition. Results: Our BLAST analysis identified several of the proteins involved in EV biogenesis in ticks, including Rab27. We show that silencing rab27 in I. scapularis impacts tick fitness. Additionally, ticks acquire less A. phagocytophilum after rab27 silencing. Experiments in the tick ISE6 cell line show that silencing of rab27 causes a distinct range profile of tick EVs, indicating that Rab27 is needed to regulate EV biogenesis. Conclusions: Rab27 is needed for successful tick feeding and may be important for acquiring A. phagocytophilum during a blood meal. Additionally, silencing rab27 in tick cells results in a shift of extracellular vesicle size. Overall, we have observed that Rab27 plays a key role in tick EV biogenesis and the tripartite interactions among the vector, the mammalian host, and a microbe it encounters. (© 2024. The Author(s).) |
التعليقات: | Update of: bioRxiv. 2023 Nov 02:2023.11.02.565357. doi: 10.1101/2023.11.02.565357. (PMID: 37961338) |
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معلومات مُعتمدة: | P01 AI138949 United States AI NIAID NIH HHS; F31 AI167471 United States AI NIAID NIH HHS; R21AI165520 United States NH NIH HHS; R01AI116523 United States NH NIH HHS; R01AI134696 United States NH NIH HHS; R21 AI165520 United States AI NIAID NIH HHS; R01AI162819 United States NH NIH HHS; F31 AI152215 United States AI NIAID NIH HHS; P01AI138949 United States NH NIH HHS; R01 AI116523 United States AI NIAID NIH HHS; F31AI167471 United States NH NIH HHS; R01 AI134696 United States AI NIAID NIH HHS; R01 AI162819 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: Extracellular vesicles; Rab27; Tick-borne diseases; Ticks |
المشرفين على المادة: | 0 (rab27 GTP-Binding Proteins) 0 (Arthropod Proteins) |
تواريخ الأحداث: | Date Created: 20240209 Date Completed: 20240214 Latest Revision: 20240625 |
رمز التحديث: | 20240625 |
مُعرف محوري في PubMed: | PMC10854084 |
DOI: | 10.1186/s13071-024-06150-7 |
PMID: | 38336752 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1756-3305 |
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DOI: | 10.1186/s13071-024-06150-7 |