Iron robbery by intracellular pathogen via bacterial effector–induced ferritinophagy
Qi Yan, Wenqing Zhang, Mingqun Lin, Omid Teymournejad, Khemraj Budachetri, Jeffrey Lakritz, Yasuko Rikihisa
Abstract
Significance Ehrlichia chaffeensis infects and proliferates inside monocytes and macrophages by acquiring iron from the cellular labile iron pool and causes a potentially fatal disease called human monocytic ehrlichiosis. This report reveals a unique bacterial iron hijacking mechanism. Ehrlichia deploys a protein Etf-3 via the bacteria type IV secretion system. Etf-3 binds ferritin and induces ferritinophagy, thereby increasing the cellular labile iron pool for Ehrlichia to acquire iron for intracellular proliferation. This, in concert with coregulation of bacterial and host cell superoxide dismutases with type IV secretion system, enables Ehrlichia to prevent reactive oxygen species–induced host cell damage mediated by labile iron. This finding unifies current concepts of intracellular bacterial infection, ferritinophagy, and ROS, which may be exploited to inhibit Ehrlichia infection.