# Regulation of VapC toxins by Ser/Thr phosphorylation of VapB antitoxins in M. tuberculosis

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2020 · $265,500

## Abstract

PROJECT SUMMARY
 The long-term goal of this research is to understand how Mycobacterium tuberculosis toxin-antitoxin
systems are regulated to contribute to tuberculosis pathogenesis. The specific goal of this R21 research
proposal is to investigate our hypothesis that Ser/Thr phosphorylation of VapB antitoxins by receptor-type
Ser/Thr protein kinases represents a novel mechanism by which VapC toxins can be regulated in response to
environmental signals. VapC toxins are the majority of all TA toxins in M. tuberculosis and have been
implicated in proteome remodeling, growth arrest, antibiotic tolerance and ability to survive a range of stresses
that are relevant for tuberculosis pathogenesis. The established role of VapB antitoxins in sequestering
cognate VapC toxin proteins and autoregulating vapBC gene expression, together with our recent finding of
significantly decreased phosphorylation of several VapB proteins in the setting of specific kinase depletion,
provide the premises for this research.
 This research proposal has two Aims. In Aim 1 we will determine the effects of phosphorylation of two
VapB antitoxins on i) the growth of M. tuberculosis expressing these antitoxins together with their cognate
VapC toxins, and ii) the molecular interactions of these VapB toxins with their cognate VapC proteins and their
cognate promoters. In Aim 2 we will investigate the effects of phosphorylation of these VapB antitoxins on
VapC enzyme activity.
 This research will test our hypothesis that VapB Ser/Thr phosphorylation may be a means to regulate
VapC activity and will begin to characterize the molecular mechanism(s) by which this regulation occurs.
Results from this research will provide the foundation for further investigation into how Ser/Thr phosphorylation
of VapB antitoxins can function to transduce signals to control the activity of VapC toxins that are relevant for
M. tuberculosis growth control, stress tolerance and tuberculosis pathogenesis.

## Key facts

- **NIH application ID:** 9978276
- **Project number:** 1R21AI146539-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ROBERT N HUSSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $265,500
- **Award type:** 1
- **Project period:** 2020-02-21 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978276

## Citation

> US National Institutes of Health, RePORTER application 9978276, Regulation of VapC toxins by Ser/Thr phosphorylation of VapB antitoxins in M. tuberculosis (1R21AI146539-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9978276. Licensed CC0.

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