Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase

Lin, Mingqun; Liu, Hongyan; Xiong, Qingming; Niu, Hua; Cheng, Zhihui; Yamamoto, Akitsugu; Rikihisa, Yasuko

E. chaffeensis and A. phagocytophilum encode a type IV secretion (T4S) system 11, [38] [39] [40] [41] that mediates the transport of bacterial DNA and/or proteins, referred to as effectors/substrates, across the bacterial membrane into the eukaryotic cell to deregulate or modulate target cell functions. 42 Ats-1 (Anaplasma translocated substrate-1), an A. phagocytophilum T4S effector, directly binds BECN1 and induces ER-derived autophagosomes that target and fuse with A. phagocytophilum inclusions to deliver host cytosolic nutrients. 37 Other than Ats-1, bacterial factors that induce autophagy to promote bacterial nutrition have not been reported. In this study, we explored roles of autophagy in E. chaffeensis infection and mechanisms by which autophagy is usurped for its replication in the early endosome-like compartment. ECH0825 (here referred to as E. chaffeensis translocated factor 1, Etf-1) is the first experimentally proven T4S effector in the genus Ehrlichia. 43 Our findings demonstrate that a unique Etf-1-induced pathway distinct from that of A. phagocytophilum has evolved in E. chaffeensis to co-opt autophagy for proliferation.