# Characterizing Notch Ligand Mimic Function of the Ehrlichia TRP120 Effector in Suppression of Host Cell Apoptosis

> **NIH NIH F31** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $34,315

## Abstract

PROJECT SUMMARY/ABSTRACT
Human monocytotropic ehrlichiosis (HME) is a tick-borne zoonosis caused by the intracellular gram-negative
bacterium, Ehrlichia chaffeensis. Since 2000, only 200 cases of ehrlichiosis were reported, however in 2017 the
number of reported cases has increased to 1,642. Notably, the number of reported cases is underestimated by
100-fold due to underreporting and underdiagnosing. HME results in patient hospitalization in 43–62% of cases
and progression of the disease can result in life threatening outcomes, including respiratory failure, meningitis,
renal failure, hepatic failure, and coagulopathies. This study aims to unmask the molecular mechanisms utilized
by E. chaffeensis to repurpose host immune defenses through pathogen mimicry of host proteins for infection
and survival. Molecular mimicry is a well-documented survival stategy utilized by pathogens. In particular, several
pathogens have evolved specific interaction motifs that mimic host motifs to facilitate host-pathogen interactions
for exploitation of host machinery. Recent studies by our laboratory have shown host-pathogen interactions to
occur through the tandem repeat protein (TRP) effector, TRP120, which is able to directly activate
Notch signaling. Notch activation has been shown to play significant roles in various other functions, including
innate immune mechanisms such as autophagy and apoptosis. Recent studies have demonstrated inhibition of
host cell apoptosis as a mechanism utilized by E. chaffeensis for survival. Activation of Notch has shown to assist
in inhibition of apoptosis by stabilizing expression of an anti-apoptotic protein, X-Linked Inhibitor of Apoptosis
(XIAP). Interestingly, TRP120 has been shown, by our laboratory, to directly interact with ADAM17, a Notch
metalloprotease, and FBW7, a Notch antagonist. Further, colocalization of TRP120 with both ADAM17 and the
Notch-1 receptor has been demonstrated. Using sequence homology databases, we have demonstrated
sequence homology of a motif in the tandem repeat domain of TRP120 (TRP120-TR) and several Notch ligands.
Moreover, we have demonstrated the TRP120-TR domain is necessary for Notch activation during E. chaffeensis
and have currently identified a 35-amino acid TRP120 Notch activation motif. We investigated expression levels
of XIAP during infection to determine if Notch activation is potentially leading to stability of XIAP. Results
demonstrated an increase in XIAP expression at later time points of infection. In the present study, which is the
next step toward achieving our main research goal, we will perform protein-protein interaction studies using
surface plasmon resonance (SPR) and atomic force microscopy (AFM) with TRP120 recombinant proteins and
synthetic peptides to define the precise TRP120 Notch ligand mimic motif and characterize TRP120-Notch
receptor interaction. We will further use in vitro studies to determine the functional role of Notch activation during
E. chaffeensis infect...

## Key facts

- **NIH application ID:** 9992341
- **Project number:** 1F31AI152424-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** LaNisha Patterson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,315
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992341

## Citation

> US National Institutes of Health, RePORTER application 9992341, Characterizing Notch Ligand Mimic Function of the Ehrlichia TRP120 Effector in Suppression of Host Cell Apoptosis (1F31AI152424-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9992341. Licensed CC0.

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