# Effector-mediated Ubiquitin Manipulation in Legionella Pneumophila Pathogenesis

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $392,377

## Abstract

Project Summary
 Active modulation of host function is essential for the success of bacterial pathogens. The ubiquitin
network regulates virtually every cellular process in eukaryote, particularly those involved in the detection,
recognition and response to infection. It is thus not unexpected that many pathogens target host
ubiquitination for their benefits. Earlier studies revealed that Legionella pneumophila, the causative agent of
Legionnaires' disease, interferes with host ubiquitin signaling by using at least 9 of its Dot/Icm effectors. Our
recent study has identified members of the SidE effector family as unique ubiquitin manipulation enzymes.
First, these proteins contain a deubiquitinase motif that attacks ubiquitinated proteins. Second, these
proteins catalyze ubiquitination by an unusual mechanism: the reaction does not require the E1, E2
enzymes or ATP, factor that are essential for all described ubiquitination events. Furthermore, these novel
ubiquitin manipulating effectors are required for maximal intracellular bacterial replication, which differs
sharply with the majority of Legionella type IV effectors. By biochemical and structural analyses, we will first
study the mechanisms of action of these proteins. We will also study the regulation of their activity by
factors from the bacterium and determine how such activity contributes to the biogenesis of the phagosome
supportive of intracellular bacterial replication. These studies will not only reveal novel mechanisms of host
function exploitation by intracellular pathogens, but also will have the potential to revise the current
understanding of ubiquitination, an enormously important signaling mechanism.

## Key facts

- **NIH application ID:** 9973136
- **Project number:** 5R01AI127465-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Zhao-Qing Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,377
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973136

## Citation

> US National Institutes of Health, RePORTER application 9973136, Effector-mediated Ubiquitin Manipulation in Legionella Pneumophila Pathogenesis (5R01AI127465-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973136. Licensed CC0.

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