Identification of Novel Anaplasma Phagocytophilum Adhesins and Receptors

Human granulocytic anaplasmosis (HGA) is an emerging, potentially lethal disease and the second most-common tick-transmitted infection of humans in the United States. HGA is caused by a bacterium, Anaplasma phagocytophi/um that also afflicts animals including dogs, sheep, and horses. After being transmitted to a human or animal by the bite of an infected tick, A. phagocytophilum invades a specific type of white blood cell called a neutrophil. The ensuing disease is characterized by symptoms that include fever, malaise, anemia, and impaired immune responses. The susceptibility of neutrophils to A. phagocytophilum is due to precise molecular interactions that occur between the bacterium and its host neutrophil. Essentially, A. phagocytophilum presents an array of "keys" (called adhesins) on its surface that interact with certain "locks" (called receptors) on the neutrophil surface. These interactions "open the door" for the bacterium to invade its host cell and cause disease. We are working to discover the A. phagocytophi/um adhesins and the neutrophil receptors that they bind as means for identifying new targets for therapies or vaccines for treating or preventing HGA, respectively. This work has potential for developing treatments against other tick-borne diseases caused by pathogens related to A. phagocytophilum.