# Function of a novel Mycobacterium tuberculosis lipase and its interaction with host proteins

> **NIH NIH R03** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2022 · $77,000

## Abstract

ABSTRACT
Tuberculosis (TB) is a worldwide public health concern because of its high morbidity and mortality. The causative
pathogen of TB, Mycobacterium tuberculosis (Mtb), has a unique mycolic acid-rich cell envelope, and can induce
accumulation of lipids in the host cells. Inside cells, it exploits host lipids as important nutrients for its infection
and long-term intracellular survival. Emerging evidences support that some lipases secreted by Mtb play vital
roles in its intracellular persistence. However, the exact functions of these Mtb-secreted lipases and mechanisms
that channel their interactions with host cytosolic proteins remain to be unraveled. Previously, we determined
that Mtb Rv1075c belongs to a GDSL-like lipase family with a deacylase activity and hydrolyzes triacetin and
tributyrin. The gene-disrupting mutation of rv1075c attenuates Mtb’s intracellular growth in macrophages and
reduces bacterial load in the infected mice. Recently, we observed that Rv1075c’s lipase activity was enhanced
when macrophage lysate was added into the enzymatic reaction, indicating that some eukaryotic factors
contribute to boosting Rv1075c’s lipase activity. Subsequently, we performed an ultimate yeast 2-hybrid to
screen for host proteins interacting with Rv1075c. We have identified that vimentin (VIM) is one of the proteins
interacting with Rv1075c. It has been reported that VIM in adipocytes forms a scaffold around lipid droplets and
VIM is a functional partner of lipase to facilitate lipolysis. Combining these evidences with our data, we
hypothesize that Mtb Rv1075c interacts with VIM that scaffolds host lipid droplets in macrophages, and the
interaction facilitates Rv1075c’s activity in lipolysis so that Mtb can utilize host lipids as energy source for its
intracellular persistence. The objective of our proposed studies is to identify mechanism of Rv1075c in the
process of accessing host lipid droplets in macrophages and determine its interaction with host VIM protein and
the impact of this interaction on Mtb intracellular growth. We will test this hypothesis by pursuing two specific
aims: 1) Identify the mechanism by which Mtb Rv1075c interacts with the eukaryotic cytosolic VIM; 2) Determine
whether the Rv1075c-VIM interaction enhances Rv1075c’s lipase and phospholipase A activity and facilitates
Mtb intracellular survival in macrophages. The proposed research will uncover mechanism of the Rv1075c-VIM
interaction and address fundamental questions about how the Rv1075c-VIM interaction affects Mtb intracellular
survival and growth. The results from these studies will expand our knowledge of Mtb’s utilization of host lipids
during infection and will lead to discovery of new mechanisms of Mtb pathogenesis.

## Key facts

- **NIH application ID:** 10352698
- **Project number:** 1R03AI166409-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Ying Kong
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $77,000
- **Award type:** 1
- **Project period:** 2022-08-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352698

## Citation

> US National Institutes of Health, RePORTER application 10352698, Function of a novel Mycobacterium tuberculosis lipase and its interaction with host proteins (1R03AI166409-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10352698. Licensed CC0.

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