# Redefining the role of autophagy in bacterial disease

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $515,124

## Abstract

PROJECT SUMMARY
In addition to traditional antimicrobials, targeting host defense pathways is an attractive strategy to limit the
adverse effect of bacterial infection. One such pathway that has received considerable attention is autophagy,
a process by which cellular constituents are sequestered in a double-membrane vesicle that is subsequently
targeted to the lysosome for degradation and recycling. Autophagy is suggested to be critical for cell
autonomous defense because many bacterial pathogens are detected within double-membrane vesicles upon
internalization. Therefore, it is possible that drugs that target autophagy will be useful in a wide range of
diseases downstream of bacterial infections. However, in addition to a direct microbicidal mechanism,
autophagy has many substrates and cell type-specific functions that may contribute to the outcome of an
infection. Thus, we chose to re-examine the role of autophagy in vivo using two model pathogens – Salmonella
enterica Typhimurium and Staphylococcus aureus. We chose to investigate S. Typhimurium because previous
in vitro studies extensively demonstrated that this bacterium is targeted for degradation through autophagy. In
contrast, in vitro experiments indicate that S. aureus uses the autophagy machinery for intracellular survival. In
preliminary data, we demonstrate that inhibiting autophagy in vivo leads to the opposite outcome that is
predicted by the literature. Specifically, autophagy mutants were protected from S. Typhimurium and
susceptible to S. aureus. The goal of this proposal is to elucidate the physiological mechanism by which
autophagy functions during infection by these two important bacterial pathogens. In Aim 1, we will test a model
in which S. Typhimurium recruits the autophagy machinery to repair the Salmonella-containing vacuole (SCV)
and evade innate immune sensors. In Aim 2, we will define a novel role for autophagy in regulating the cell
surface proteome of the host cells, a function that is critical in limiting damage caused by a pore-forming toxin
produced by S. aureus. The results from the proposed experiments will challenge the existing paradigm on the
role of autophagy in antimicrobial defense and guide the proper use of drugs that target autophagy.

## Key facts

- **NIH application ID:** 10053295
- **Project number:** 5R01AI121244-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ken Hashigiwa Cadwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $515,124
- **Award type:** 5
- **Project period:** 2016-11-10 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053295

## Citation

> US National Institutes of Health, RePORTER application 10053295, Redefining the role of autophagy in bacterial disease (5R01AI121244-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10053295. Licensed CC0.

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