# The requirement for PDIM in mycobacterial protein secretion

> **NIH NIH R03** · UNIVERSITY OF NOTRE DAME · 2020 · $78,167

## Abstract

PROJECT SUMMARY:
The mechanism of mycobacterial protein secretion remains elusive. The long-term goal of the applicant is to
understand the molecular mechanisms of mycobacterial protein secretion. The overall objective of this applica-
tion is to rigorously determine if the outer lipid, PDIM (phthiocerol dimycocerosate), is required for protein secre-
tion. The central hypothesis is that PDIM promotes the optimal secretion of mycobacterial proteins across the
MOM (mycobacterial outer membrane). The rationale underlying this proposal is that the successful completion
of the proposed work will potentially inform the elusive mechanisms of protein secretion across the envelope
while resolving an open question in the field regarding the role of PDIM in protein secretion. The central hypoth-
esis will be tested by following this specific aim: Define the requirement for PDIM biosynthesis and transport in
protein secretion. Under this aim, a combination of genetics with targeted and global quantitative proteomics will
be used to measure changes in protein secretion in the presence or absence of PDIM production and localiza-
tion. The expected outcome following the successful completion of the proposed aim will be the definitive deter-
mination of the requirement of PDIM in mycobacterial protein secretion. This contribution will be significant be-
cause it will directly inform the elusive mechanism of mycobacterial protein secretion and potentially identify the
ESX-1 substrates that promote membrane lysis, advancing the field vertically. Moreover, completion of this pro-
posal will contribute fundamental knowledge that could positively impact the treatment and prevention of the
human disease, tuberculosis. The proposed research is conceptually innovative because it focuses on protein
secretion independent of a class secretory apparatus. Moreover, the proposal provides an innovative explanation
which could unify two disparate studies in the literature regarding the role of PDIM in protein secretion. Defining
the relationship of the outer lipid PDIM with secretion will advance the field vertically by providing new insight
into the molecular mechanisms of mycobacterial protein secretion.

## Key facts

- **NIH application ID:** 10047762
- **Project number:** 1R03AI149147-01A1
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Patricia A Champion
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,167
- **Award type:** 1
- **Project period:** 2020-06-08 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10047762

## Citation

> US National Institutes of Health, RePORTER application 10047762, The requirement for PDIM in mycobacterial protein secretion (1R03AI149147-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10047762. Licensed CC0.

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