# Membrane Interaction of Mycobacterium tuberculosis Virulence Factors

> **NIH NIH SC1** · UNIVERSITY OF TEXAS EL PASO · 2020 · $339,750

## Abstract

Title: Membrane interaction of Mycobacterium tuberculosis virulence factors
PROJECT SUMMARY
 It is estimated that Mycobacterium tuberculosis (Mtb), a contagious and airborne bacterial pathogen,
infects one-third of the world population and causes 1-2 million deaths each year. It is believed that initial Mtb
infection occurs in alveolar macrophages. Mtb is internalized into the phagosome, where it penetrates the
phagosomal membrane and translocates into the cytosol for replicating and cell-to-cell spreading. The
cytosolic translocation is regarded as an important mechanism of Mtb pathogenesis. Two Mtb virulence
factors, namely 6-kDal early antigenic target (MtbESAT6) and 10-kDal culture filtrate protein (MtbCFP10), are
secreted out of Mtb as a heterodimer and have been implicated to play an essential role in Mtb cytosolic
translocation. Genetic knockout of either esat-6 or cfp-10 results in defective cytosolic translocation and
attenuated virulence. Our recent studies have suggested that MtbESAT-6 has an acidic-pH dependent pore-
forming activity that is required for Mtb cytosolic translocation and virulence. However, the molecular
mechanisms governing MtbESAT-6 pore formation and heterodimer dissociation are not clear. In the present
proposal, using a variety of biochemical, microscopic, structural and cellular approaches, we will probe the
dynamic process of MtbESAT-6 pore formation and determine the structure of the pore complex. We will also
investigate the role of Nα-acetylation of MtbESAT-6 in acidification-induced heterodimer dissociation, a
prerequisite for MtbESAT-6 to interact with the membrane. Studies designed in this grant proposal are aimed
to fill the critical gap in our understanding of the MtbESAT-6-dependent molecular events during Mtb infection
in alveolar macrophages and other phagocytes. Knowledge obtained from the proposed studies will facilitate
the development of novel countermeasures, therapeutics and vaccines, against tuberculosis.
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## Key facts

- **NIH application ID:** 9902488
- **Project number:** 5SC1GM095475-09
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Jianjun Sun
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,750
- **Award type:** 5
- **Project period:** 2011-04-08 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902488

## Citation

> US National Institutes of Health, RePORTER application 9902488, Membrane Interaction of Mycobacterium tuberculosis Virulence Factors (5SC1GM095475-09). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9902488. Licensed CC0.

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