# Structural characterization of MCE transport systems from Mycobacterium tuberculosis

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $132,859

## Abstract

Project Summary/Abstract
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is one of the deadliest pathogens
on the planet, and for decades, TB has been the leading cause of death due to infectious disease. The cell
envelope of Mtb forms a notoriously tough barrier around the cell, protecting the bacterium from harsh agents
in the environment such as antibiotics and host immune responses. At the same time, Mtb imports nutrients
from the host cell, such as cholesterol, across the cell envelope. Transport of lipids, metabolites and nutrients
across the cell envelope, between the inner and outer membranes is critical for building and maintaining the
cell envelope itself, and for import of key factors required for bacterial growth. Therefore, the transport systems
that facilitate this trafficking are critical for allowing Mtb to survive and thrive in its intracellular niche, most
typically macrophages in the lungs.
 The MCE (Mammalian Cell Entry) family of proteins are transport systems that have been implicated as
virulence factors in Mtb, and are an expanded protein family in mycobacteria compared with other
double-membraned bacteria. In Mtb, several lines of evidence suggest that MCE systems are important for
importing nutrients such as cholesterol and fatty acids. Recent work on E. coli MCE systems has shown that
these are multi-protein complexes anchored in the inner membrane of double-membraned bacteria, and may
play an important role in the maintenance of outer membrane integrity, raising the possibility that this may also
be a role that MCE proteins play in Mtb. The structure and mechanisms of the highly complex MCE systems in
Mtb remain unknown, and studying these is critical for understanding how MCE systems work, what their
substrates are, and how they may be linked to virulence.
 This proposal is focused on biochemical and structural characterization of MCE transport systems from
Mtb and the non-pathogenic model, Mycobacterium smegmatis. Using single particle cryo-EM, mass
spectrometry, biochemical and functional assays, we aim to study the structure and function of endogenous
Mtb MCE systems, decipher which protein subunits come together to form complexes and define
protein-protein interactions that are important for the systems to assemble and function. The results of this
work will provide important insights into the structure and function of the large, multi-protein MCE complexes in
the Mtb cell envelope, and how they influence replication and virulence in the host.

## Key facts

- **NIH application ID:** 10775835
- **Project number:** 5R01AI174646-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Gira Bhabha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,859
- **Award type:** 5
- **Project period:** 2023-02-03 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775835

## Citation

> US National Institutes of Health, RePORTER application 10775835, Structural characterization of MCE transport systems from Mycobacterium tuberculosis (5R01AI174646-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10775835. Licensed CC0.

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