# Defining the impact of membrane vesicle deficiency on M. tuberculosis-macrophage interactions

> **NIH NIH R03** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $78,459

## Abstract

Summary
Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB) in humans, releases
extracellular vesicles in vitro and in vivo. Like extracellular vesicles released by Gram-positive bacteria
mycobacterial extracellular vesicles originate at the plasma membrane and are therefore, refer to as
membrane vesicles (MV). Mycobacterial MVs contain a broad range of immunologically active proteins
and glycolipids. When added to cells in culture, isolated MVs can regulate the immune response of
uninfected macrophages, T-cells and dendritic cells. However, the influence of MVs on the interaction(s)
between Mtb and the infected macrophage and the overall relevance of MVs production during infection
is unclear, mainly because MV-deficient Mtb mutants have not yet been described. It has been
recognized that MV biogenesis in M. tuberculosis is an active and regulated process, but the molecular
mechanisms and factors involved remain largely unknown.
Our previous work demonstrated that iron limitation, a condition encountered in the host, induces the
production of MVs in Mtb. Preliminary studies based on this finding identified a pair of iron-responsive,
mycobacterial dynamin-like protein (DLP)-encoding genes, isoniazid‐inducible gene A and C (iniAC) that
are necessary for MV production. Our preliminary data indicate that a DLP null mutant grows normally in
low-iron conditions and in macrophages. However, it exhibits a substantial defect in MV biogenesis. We
postulate that this mutant will help define the role of MVs in immunomodulation and pathogenic
interactions with the host. The proposed research will test our central hypothesis that MV production
during macrophage infection requires the DLPs IniAC and that comparison of the immune response
associated with macrophages infected with WT Mtb or the MV-deficient iniAC mutant will reveal
substantial differences.
The outcome of this project will increase understanding of MV biogenesis in Mtb and its relevance during
macrophage infection, and provide the foundation for in vivo studies that evaluate the relevance of MVs
at the Mtb-host interface.

## Key facts

- **NIH application ID:** 10176403
- **Project number:** 5R03AI153560-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Gloria Marcela Rodriguez
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,459
- **Award type:** 5
- **Project period:** 2020-06-04 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176403

## Citation

> US National Institutes of Health, RePORTER application 10176403, Defining the impact of membrane vesicle deficiency on M. tuberculosis-macrophage interactions (5R03AI153560-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176403. Licensed CC0.

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