# Modulation of Host Cell Environment by Mycobacterial PE/PPE Proteins

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $553,259

## Abstract

Abstract
Autophagy, a key host defense pathway, has an essential role in both innate and adaptive immunity. However,
many microbes have evolved mechanisms to evade, subvert, or exploit autophagy. Bacterial and viral
pathogens can block autophagosome fusion with lysosomes to evade degradation, or utilize nutrients in such
vesicles. It has been demonstrated that stimulation of autophagic pathways in macrophages causes
mycobacterial phagosomes to mature into phagolysosomes, which can then overcome the trafficking block
imposed by Mycobacterium tuberculosis. Thus, induction of autophagy can suppress intracellular survival of
mycobacteria. We hypothesize that mycobacterial virulence factors mediate autophagy evasion in order to
ensure survival within the infected macrophages. The identification and characterization of such virulence
factors will allow us to understand the mechanisms by which autophagy affects the outcome of host-microbe
interactions and immune responses. Through loss-of-function screening of mycobacteria using transposon
mutant screening, we were able to identify thirteen chromosomal regions responsible for manipulating
mycobacterial infection-induced autophagy. Remarkably, six of these regions contain genes belonging to the
PE/PPE protein family that are especially abundant in pathogenic mycobacteria and have been shown to play
diverse roles in mycobacterial pathogenesis and in modulating critical innate immune pathways. However, no
PE/PPE proteins are known to be associated with autophagy pathways. Thus, the goals of this project are to
investigate the roles and mechanisms of a subset of PE/PPE proteins and to determine the consequences of
autophagic degradation of mycobacteria on innate and adaptive immunity. Increased knowledge of M.
tuberculosis infection-induced autophagy presents an opportunity to uncover new and promising therapeutics
against tuberculosis to prevent mycobacterial infection and survival within the host. Additionally, the pro-
autophagic mutants generated in this study may have significant application in the development of effective,
safe and persistent TB vaccines.

## Key facts

- **NIH application ID:** 10064574
- **Project number:** 5R01AI127711-05
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Sunhee Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $553,259
- **Award type:** 5
- **Project period:** 2016-12-09 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064574

## Citation

> US National Institutes of Health, RePORTER application 10064574, Modulation of Host Cell Environment by Mycobacterial PE/PPE Proteins (5R01AI127711-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064574. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*