Ehrlichia chaffeensis Etf-3 Induces Host RAB15 Upregulation for Bacterial Intracellular Growth.

Autor: Yang N; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Li M; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Qin S; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Duan N; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Li X; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Zhou Y; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Wang M; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Jin Y; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Wu W; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China., Cheng Z; The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.; Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Feb 22; Vol. 25 (5). Date of Electronic Publication: 2024 Feb 22.
DOI: 10.3390/ijms25052551
Abstrakt: Ehrlichia chaffeensis infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, E. chaffeensis resides in membrane-bound inclusions, E. chaffeensis -containing vesicles (ECVs), which have early endosome-like characteristics and fuse with early autophagosomes but not lysosomes, to evade host innate immune microbicidal mechanisms and obtain nutrients for bacterial intracellular growth. The mechanisms exploited by E. chaffeensis to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied. Here, we demonstrate that E. chaffeensis type IV secretion system (T4SS) effector Etf-3 induces RAB15 upregulation in host cells and that RAB15, which is localized on ECVs, inhibits ECV fusion with lysosomes and induces autophagy. We found that E. chaffeensis infection upregulated RAB15 expression using qRT-PCR, and RAB15 was colocalized with E. chaffeensis using confocal microscopy. Silence of RAB15 using siRNA enhanced ECV maturation to late endosomes and fusion with lysosomes, as well as inhibited host cell autophagy. Overexpression of Etf-3 in host cells specifically induced RAB15 upregulation and autophagy. Our findings deepen the understanding of E. chaffeensis pathogenesis and adaptation in hosts as well as the function of RAB15 and facilitate the development of new therapeutics for HME.
Databáze: MEDLINE
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