# The Anti-Autophagy Arsenal of Legionella pneumophila

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $43,094

## Abstract

PROJECT SUMMARY
 Autophagy is a highly conserved, primarily degradative pathway defined by the growth of a cup-shaped
membrane that envelopes and delivers cytosolic cargo (such as bacteria) to the lysosome for degradation.
Legionella pneumophila is a species of facultative intracellular bacteria that secretes over 300 effector proteins
that subvert host pathways such as the degradative endosomal and autophagy pathways to promote
intracellular survival. Legionella lacking currently known autophagy-inhibiting effectors are still capable of
evading this pathway, indicating that there are additional, undiscovered autophagy-inhibiting effectors. Taking
advantage of the highly conserved nature of this pathway, a recent screen identified several Legionella
effectors that blocked autophagy in yeast. One of those effectors, Lem26, was confirmed to inhibit autophagy
in mammalian cells. With the central hypothesis that Lem26 inhibits autophagy to prevent the capture
and lysosomal degradation of Legionella, the proposed research is designed to identify the mechanism by
which Lem26 inhibits autophagy (Aim 1) and determine its physiological relevance in the context of infection
(Aim 2). To discover the mechanism by which Lem26 inhibits autophagy, Aim 1 utilizes both an unbiased mass
spectrometry-based approach to identify the host targets of Lem26 as well as targeted experimentation on
putative targets based on epistasis data identifying the autophagic step inhibited by Lem26. To determine the
physiological relevance of Lem26 in the context of infection, Aim 2 utilizes multiple approaches to identify the
localization and interactome of bacterially translocated Lem26 as well as assess the impact of Lem26 on the
progression of autophagy and the intracellular growth of Legionella. The research and training plans laid out in
this proposal will be executed in a highly collaborative environment that is suited for the development of the
critical thinking skills and technical expertise required for a future research group leader. Given the broad
implication of autophagy in various diseases and the common virulence strategies employed by intracellular
pathogens, this proposed work will have broad implications in human disease.

## Key facts

- **NIH application ID:** 10817024
- **Project number:** 5F31AI169882-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kevin Reyes Parducho
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,094
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817024

## Citation

> US National Institutes of Health, RePORTER application 10817024, The Anti-Autophagy Arsenal of Legionella pneumophila (5F31AI169882-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10817024. Licensed CC0.

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