# A novel protein export chaperone of Mycobacterium tuberculosis

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2024 · $508,167

## Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), represents a severe world health
crisis (4,000 TB deaths daily). A better understanding of Mtb biology and pathogenesis will drive development
of novel strategies to control the TB epidemic. In bacterial pathogens, like Mtb, many proteins are exported to
the bacterial cell envelope or the extracellular environment in order to carry out critical functions in bacterial
physiology, virulence or immune responses. Thus, Mtb pathways that export proteins could be targeted or
exploited for the development of novel anti-TB control measures. However, significant gaps exist in our
understanding of Mtb protein export.
 This proposal is to determine the mechanism of SatS, a novel protein export chaperone we discovered
in Mtb. SatS is a chaperone for a subset of proteins that are exported by the specialized SecA2 protein export
pathway, and SatS is required for intracellular growth of Mtb in macrophages. However, SatS shares no
sequence or structural similarity with any previously characterized proteins and the mechanism of SatS is
completely unknown. Substrate specificity and the scope of SatS substrates are also unknown. Aim 1 of this
proposal is to determine the mechanistic details of SatS function in protein export. Aim 2 is to determine the
structures of SatS and that of SatS in complex with peptides of substrates. Aim 3 is to identify SatS-binding
sites in substrates and to identify additional SatS substrates. By completing these Aims, we will determine the
mechanism and contribution of SatS to Mtb protein export and biology. More broadly, these studies will
improve our understanding of bacterial strategies for exporting proteins and of the diversity of molecular
chaperones across biological systems. Long-term, the results could lead to strategies for inhibiting protein
export as a novel anti-TB therapy. Alternatively, the knowledge gained could be harnessed to engineer
mycobacterial strains with improved capacity to export proteins for use as experimental tools or as live,
attenuated vaccines with enhanced antigen export.

## Key facts

- **NIH application ID:** 11001046
- **Project number:** 7R01AI149727-05
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Miriam S. Braunstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $508,167
- **Award type:** 7
- **Project period:** 2024-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11001046

## Citation

> US National Institutes of Health, RePORTER application 11001046, A novel protein export chaperone of Mycobacterium tuberculosis (7R01AI149727-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11001046. Licensed CC0.

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