# Characterization of the nutrient assimilation pathways in M. tuberculosis

> **NIH NIH R01** · CORNELL UNIVERSITY · 2021 · $571,814

## Abstract

Project Summary / Abstract
 Mtb utilizes host-derived lipids to promote pathogenesis and this is a defining feature of this intracellular
pathogen. During infection Mtb imports and metabolizes host lipids to support pathogenesis by producing: i)
energy, ii) central metabolic intermediates, or iii) polyketide virulence lipids. While the metabolic pathways in Mtb
that degrade or process lipids are complex and contain redundant enzymes, the bacterial Mce lipid transporters
appear to be specific for dedicated lipid substrates.
 Aim 1 of this work proposes to employ genetic and biochemical approaches to identify and characterize novel
gene/proteins required for fatty acid import in Mtb. While it is understood that Mce1 imports fatty acids, the
substrate specificity of this transporter is unknown. Therefore, we intend to define substrates and the biochemical
basis of Mce1 substrate specificity. Our preliminary studies indicate that Mtb transports fatty acid precursors of
immune signaling lipids via Mce1 and we include here studies to evaluate if scavenging of this immune lipid
precursors by Mtb impacts the immune response.
 Aim 2 proposes to identify and characterize protein subunits that are shared by all the Mce transporters and
are required for lipid import in Mtb. We have determined that LucA is required for Mce1- and Mce4-mediated
transport and LucA stabilizes these transporter complexes. These studies seek to characterize the basis for this
transporter stabilization. Similarly, MceG is required for Mce1- and Mce4-mediated transport and we intend to
understand how MceG stabilizes and interacts with Mce1. We will use a genetic approach to silence LucA and
MceG in Mtb within chronically infected mice and quantify bacterial fitness to determine the therapeutic potential
of drugs that potentially block these proteins.

## Key facts

- **NIH application ID:** 10120786
- **Project number:** 1R01AI150916-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Brian C VanderVen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $571,814
- **Award type:** 1
- **Project period:** 2020-11-19 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120786

## Citation

> US National Institutes of Health, RePORTER application 10120786, Characterization of the nutrient assimilation pathways in M. tuberculosis (1R01AI150916-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120786. Licensed CC0.

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