# Transporter function of the Mycobacterium tuberculosis PE/PPE proteins

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $907,773

## Abstract

ABSTRACT
Mycobacterium tuberculosis (Mtb) is surrounded by one of the thickest and most impenetrable cell walls of any
known bacterium. This structure is not unlike that of the outer membrane of gram-negative bacteria but creates
a far more extreme permeability barrier for nutrients. Other bacterial species with such an outer membrane
generally have porins that allow uptake of water-soluble nutrients, but Mtb and most pathogenic mycobacteria
do not. The mechanisms by which Mtb transports nutrients across the outer membrane in the absence of
classical porins remain largely unknown. The absence of porins in mycobacterial species is strikingly well
correlated with an expansion of proteins belonging to the Pro-Glu (PE) and Pro-Pro-Glu (PPE) protein families.
These PE/PPE proteins have been one of the most perplexing puzzles in tuberculosis biology: The 169 family
members are scattered throughout the genome, take up ~10% of Mtb’s genetic coding capacity, and are almost
exclusively found in pathogenic mycobacteria. Their sequences are highly unusual and characterized by
intrinsically disordered repeat regions. Their large number, disordered structure, and unusual length has made
the PE/PPE proteins equally difficult to work with by genetic, structural, and biochemical approaches. Over
twenty years after their discovery, they remain some of the most intractable proteins and their function remains
largely unknown. We and others now discovered an unexpected function of a subset of the PE/PPE proteins as
nutrient transporters across the outer membrane of Mtb. Here, we will test the hypothesis that the PE/PPE
proteins are a large family of transporters that shuttle nutrients across the Mtb outer membrane and that might
also be responsible for drug uptake and efflux, thus affecting Mtb drug resistance.

## Key facts

- **NIH application ID:** 10792136
- **Project number:** 1R01AI180452-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Christoph Grundner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $907,773
- **Award type:** 1
- **Project period:** 2024-02-06 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792136

## Citation

> US National Institutes of Health, RePORTER application 10792136, Transporter function of the Mycobacterium tuberculosis PE/PPE proteins (1R01AI180452-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10792136. Licensed CC0.

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