# The role and fate of Mtb storage lipids LCTAG and MWE

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $244,067

## Abstract

SUMMARY
 Tuberculosis is one of the leading causes of death due to infectious disease despite the availability of anti-
tubercular drugs. The majority of M. tuberculosis (Mtb) infections result in latent TB where bacteria have
altered metabolism and exhibit phenotypic drug tolerance. The biological pathways used to maintain metabolic
homeostasis and then fuel resuscitation and replication are poorly understood.
 A crucial component of dormancy or quiescence is the storage of carbon and energy sources in cell wall
lipids that can be recycled upon resuscitation. Mtb generates the “storage lipids” triacylglycerol (TAG) and wax
esters (WE) in late stationary phase and in response to stresses commonly associated with dormancy. During
the transition to active replication, it is believed that these lipids are mobilized and employed as a metabolic
resource. However, this has not been experimentally demonstrated. We recently described the Very Long-
Chain triacylglycerol (LCTAG) and mycolate wax ester (MWE) of Mtb. These lipids are exported from the
cytoplasm to the mycobacterial outer membrane or capsule by the MmpL11 transporter. The fates of LCTAG
and MWE once they are extracellular are not known. However, correct localization of LCTAG and MWE is
important for Mtb virulence and physiology since 1) MmpL11 is required for virulence and 2) the Mtb mmpL11
mutant has reduced resuscitation from an in vitro non-replicating persistence model. As storage lipids, surface-
localized LCTAG and MWE may be utilized as a shared resource to maintain viability and resuscitate from
non-replicating persistence.
Based on our data, we hypothesize that Mtb hydrolyzes, imports and utilizes exported storage lipids to
promote resuscitation from hypoxic and nutrient-restricted environments.
 We propose to test this hypothesis by 1) Determining how LCTAG and MWE contribute to Mtb
resuscitation from non-replicating persistence, and 2) Define proteins involved in the LCTAG and MWE
biosynthesis and recycling pathway. This exploratory study combines unbiased approaches with genetic and
biochemical analyses to investigate the important biological process of Mtb cell envelope remodeling in
metabolism.

## Key facts

- **NIH application ID:** 9893601
- **Project number:** 1R21AI144658-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Georgiana E. Purdy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $244,067
- **Award type:** 1
- **Project period:** 2020-03-23 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893601

## Citation

> US National Institutes of Health, RePORTER application 9893601, The role and fate of Mtb storage lipids LCTAG and MWE (1R21AI144658-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893601. Licensed CC0.

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