Adaptation of Anaplasma phagocytophilum to the tick vector is controlled by the transcriptional regulator Tr1

Rickettsial pathogens are strictly dependent on the cellular biology of their hosts for survival and replication. Predominantly transmitted by blood-feeding arthropods, these vector-borne pathogens are forced to adapt between the disparate environments of their mammalian host and arthropod vector. To achieve this, the Rickettsial bacteria Anaplasma phagocytophilum undergoes extensive transcriptional reprogramming with over 41% of its genes differentially transcribed between mammals and Ixodes scapularis ticks. How the bacterium orchestrates this dramatic transcriptional reprogramming is not understood. The gene tr1 encodes a Helix-Turn-Helix DNA-binding protein that is exclusively expressed during tick infection. Herein, we show that tr1 is essential for A. phagocytophilum survival in ticks and regulates the transcription of other genes necessary to adapt to the arthropod vector. We demonstrate that Tr1 is a DNA-binding protein and recognizes promotors of tick-specific genes in A. phagocytophilum, including secreted effector ateA, alternate components of type IV secretion system (T4SS), and membrane proteins. Our findings demonstrate that Tr1 is a master regulator of genes that are critical for A. phagocytophilum adaptation to the tick.