Many bacterial pathogens exploit host actin cytoskeleton either during entry/internalization or spread from cell to cell. Pathogen use of the actin cytoskeleton in arthropod vectors has not yet been explored. Using Ixodes scapularis ticks and Anaplasma phagocytophilum (the agent of human granulocytic anaplasmosis) as an infection model, I provide evidence for the first time to show how an obligate intracellular bacterium can exploit the actin cytoskeleton to control arthropod gene transcription for its own benefit. My preliminary results show that A. phagocytophilum induces the phosphorylation of tick actin and subsequently alters the ratio of monomeric/filamentous (G/F)-actin. I also show that A. phagocytophilum-induced actin phosphorylation is dependent on Ixodes PAK1-PI3kinase signaling. A. phagocytophilum-induced actin phosphorylation resulted in increased nuclear G-actin and phosphorylated actin that associated with RNA Polymerase II (RNAPII). Induced actin phosphorylation in the nucleus enhanced binding of TATA-box-binding-protein to RNAPII and caused the selective regulation of salp16, a gene crucial for A. phagocytophilum survival. This project proposal explores to identify the mechanism by which selective regulation of salp16 promoter is mediated upon A. phagocytophilum infection. Additional studies are proposed to identify whether any of the bacterial component(s) or other Ixodes transcriptional activator(s) are involved in this specific gene regulation. Collectively, this study may provide evidence for a novel role of actin phosphorylation during host- pathogen interaction and suggest new strategies to interfere with the life cycle of this obligate intracellular pathogen, and perhaps other Rickettsia-related microbes of medical importance.
In United States, Ixodes scapularis ticks transmit several human pathogens including A. phagocytophilum, the agent of human anaplasmosis. The molecular mechanisms that this bacterium uses to survive in its vector host are currently not understood. This project proposal provides evidence for a novel role of actin during host-pathogen interaction and suggests new strategies to interfere with the life cycle of this obligate intracellular pathogen, and perhaps other arthropod-borne microbes of medical importance.
|Neelakanta, Girish; Sultana, Hameeda (2015) Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases. Arch Immunol Ther Exp (Warsz) 63:169-79|