# Exploring Tr1-regulated transcription networks underpinning adaptation of pathogenic Anaplasma to the tick host

> **NIH NIH R21** · WASHINGTON STATE UNIVERSITY · 2024 · $163,213

## Abstract

Project Summary
 Tick-borne diseases are on the increase and are responsible for nearly all of the vector-transmitted disease
in the US. Vector-borne pathogens face the dual challenge of adaptation to two very different host
environments: the arthropod vector and the mammalian host. Ticks contain distinct physiological cues
including disparities in body temperature, nutrient availability, physiological architecture, and unique
immunological pressures. Once in the tick, A. phagocytophilum must further adapt to construct a replicative
niche within the arthropod’s cells. In response to the tick environment, A. phagocytophilum differentially
transcribes 41% of its genes when infecting tick cells in comparison to mammalian cell culture. It is not known
what controls this extensive reprogramming or how it facilitates A. phagocytophilum adaptation to the tick. One
predicted transcription factor, tr1, displays the highest tick-specific expression of all A. phagocytophilum genes.
Our structural modeling identifies Tr1 as a homo-dimeric helix-turn-helix DNA binding protein in the xenobiotic
response element family of transcription factors. Disruption of tr1 by transposon insertion had no impact on
bacterial burden in mice or growth in human cell lines. However, A. phagocytophilum lacking tr1 was greatly
attenuated for acquisition by ticks and is unable to survival in tick cells. Given the importance of Tr1 for survival
in the arthropod vector and its predicted role as a transcriptional switch, we hypothesize that: Tr1 operates as a
master regulator for tick adaptation by orchestrating the expression of tick-specific gene networks. In this study
we will identify the DNA sequences bound by Tr1 and its mode of transcription regulation. Further, we will
identify how Tr1 contributes to completion of the tick cell infection cycle and measure how Tr1 remodels the A.
phagocytophilum transcriptome during tick cell infection. Revealing how A. phagocytophilum adapts to infect
tick cells will open the door to development of vector targeted interventions to reduce transmissibility of the
pathogen.

## Key facts

- **NIH application ID:** 10874597
- **Project number:** 5R21AI178392-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Jason Michael Park
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,213
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874597

## Citation

> US National Institutes of Health, RePORTER application 10874597, Exploring Tr1-regulated transcription networks underpinning adaptation of pathogenic Anaplasma to the tick host (5R21AI178392-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10874597. Licensed CC0.

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