Etf-3 Induces Host Upregulation for Bacterial Intracellular Growth.

infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, resides in membrane-bound inclusions, -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 to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied. Here, we demonstrate that type IV secretion system (T4SS) effector Etf-3 induces upregulation in host cells and that RAB15, which is localized on ECVs, inhibits ECV fusion with lysosomes and induces autophagy. We found that infection upregulated expression using qRT-PCR, and RAB15 was colocalized with 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 upregulation and autophagy. Our findings deepen the understanding of pathogenesis and adaptation in hosts as well as the function of RAB15 and facilitate the development of new therapeutics for HME.