# Mycobacterium tuberculosis-mediated modulation of host immune cell metabolism

> **NIH NIH F30** · COLORADO STATE UNIVERSITY · 2020 · $50,520

## Abstract

Project Summary / Abstract
Objectives: This application seeks to train a dual degree DVM/PhD student, enhancing the student's skills in
research and clinical veterinary medicine. The project proposed in this application will prepare this student for a
career as an independent clinician-scientist in translational medical fields. Specifically, the research proposal in
this application will address critical knowledge gaps in the understanding of Mycobacterium tuberculosis (Mtb)
mediated shifts in host immune cell metabolism. Knowledge gained through this proposal will have
translational applications to other mycobacterial diseases of animals and humans.
Specific Aims: 1. Determine if mycobactin activates HIF-1α in a hypoxia-independent manner during early
Mtb infection. 2. Determine if blocking glycolysis and mitochondrial fatty acid oxidation alters Mtb survival,
macrophage viability, and Mtb-macrophage metabolomic profiles during early infection.
Research Design and Methods: 1. Using mycobactin knock-out strains of Mtb, HIF-1α morpholino oligomers,
and custom Agilent Extracellular Flux Analyzer protocols, guinea pig bone marrow derived macrophages
(GpBMDMs), will be assessed for the effect of mycobactin on HIF-1α activation and changes in cell
metabolism. WB, qRT-PCR, and Agilent protocols will be employed. Guinea pigs infected with knock-out and
control Mtb strains will be sampled for bronchoalveolar lavage and tissues (lung, spleen, lymph node) post-
mortem to complement in vitro results and to be analyzed in the same manner. 2. Targeted metabolomics
analysis of carbohydrates, fatty acid, and amino acid profiles for Mtb infected and uninfected GpBMDMs will be
compared. Two key metabolic pathways, glycolysis and mitochondrial fatty acid oxidation, will be inhibited and
the effect of altered metabolism on infection outcome will be characterized by pairing metabolomic analyses
with macrophage viability (Trypan Blue exclusion assay) and Mtb survival (CFU) data.
Relatedness to Public Health: Mtb is the leading cause of death by an infectious disease worldwide and
remains a prominent global health concern. More effective alternative approaches are needed to combat
tuberculosis in endemic areas. Host-directed therapies (HDTs), which aim to modulate the host immune and
metabolic response rather than target the pathogen, are a promising new area of study. This proposal will
contribute to the knowledge of mechanisms by which Mtb infection modulates host immune cell metabolism.
Understanding these mechanisms can aid in determining targets for HDTs and provide knowledge for the
development of novel therapeutic strategies.

## Key facts

- **NIH application ID:** 9962994
- **Project number:** 5F30OD024647-03
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Dilara Kiran
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-07-05 → 2020-07-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962994

## Citation

> US National Institutes of Health, RePORTER application 9962994, Mycobacterium tuberculosis-mediated modulation of host immune cell metabolism (5F30OD024647-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9962994. Licensed CC0.

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