# Discovering lipid transport mechanisms in Mycobacterium tuberculosis

> **NIH AI K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2026 · $135,532

## Abstract

PROJECT SUMMARY: Mycobacterium tuberculosis (Mtb) is the leading cause of death worldwide due to a
single pathogen. Mtb is exceptionally reliant on specialized lipids, yet little is known about how lipids and lipid-
linked glycans transit across the membranes and aqueous periplasm of mycobacteria. My objective is to reveal
how Mtb controls the localization and effects of important lipidic antigens, virulence factors, and cell envelope
components. I found that one of the primary mycobacterial lipid transport systems, Mce4, is not restricted to
exogenous lipid import as previously thought, but maintains steady-state levels of hundreds of native
mycobacterial lipids. I will define how periplasm-spanning Mce channels mediate directional lipid transport in
Mtb, using unbiased lipidomic methods, a new reverse micelle separation technique, and collisional mass
spectrometry. This will push the field beyond previous studies of selected exogenous lipids, and will identify the
roles that Mce channels play in native lipid transport within laboratory and clinical strains of Mtb. I also found
that the putative transport lipid mannosyl phosphomycoketide (MPM) is covalently linked to one or more Mtb
glycans, and that the gene pks12—which is required for the synthesis of MPM—is important for glycan
localization. This suggests that MPM is at the center of an undiscovered lipoglycan transport mechanism. I will
uncover this mechanism through chromatography and mass spectrometry-based identification of MPM-linked
glycans. Through the same methods along with electron microscopy and glycan labeling, I will determine the
effects of pks12 on exported Mtb glycans. I will finish by determining the role that pks12 and glycans play in a
growth defect I discovered, thereby providing a mechanistic basis for the likely in vivo essentiality of pks12 in
human disease. This proposed investigation of understudied Mtb lipid and lipoglycan transport will address a
critical knowledge gap that hinders dev

## Key facts

- **NIH application ID:** 11281440
- **Project number:** 1K99AI196044-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Gregory Hunter Babunovic
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $135,532
- **Award type:** 1
- **Project period:** 2026-04-20T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11281440

## Citation

> US National Institutes of Health, RePORTER application 11281440, Discovering lipid transport mechanisms in Mycobacterium tuberculosis (1K99AI196044-01). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11281440. Licensed CC0.

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