# Defining the role of toxin-antitoxin systems in persistence of Burkholderia pseudomallei

> **NIH NIH R21** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $197,500

## Abstract

Project Summary/Abstract
There is an urgent need to combat infections caused by Burkholderia pseudomallei, the bacterial agent
responsible for the disease melioidosis. Melioidosis is a health threat in tropical endemic regions of the world
and is now recognized as an emergent disease in areas considered non-endemic. In addition to causing acute
infections that are considered lethal if left untreated, the bacteria can persist in the host and produce very
difficult to treat latent infections. Therefore, our long-term goal is to develop effective treatments against
melioidosis and prevent latent or chronic disease outcomes. In this project, we will evaluate the function of a
subset of toxin-antitoxin systems that have been identified as one of the bacterial switches that sense stress
and activate a persistence phenotype. We will determine their association with bacterial persistence both in
vitro and in vivo. Our central hypothesis is that selective toxins are upregulated in vivo in response to specific
conditions, and loss of their function results in reduced host-associated persistence. It is important to point out
that current antibiotics used against B. pseudomallei generate persister frequencies of up to 50%. Because
current treatments last months due to the propensity of B. pseudomallei to generate latent infections, the study
of toxin-antitoxin systems can help identify new drug targets and therefore improve antibiotic efficacy. Our
proposed experimental approach will focus on two specific aims: first, we will evaluate the role of selected
toxins in survival and induction of a persistent stage during B. pseudomallei infection of macrophages because
this cell type likely facilitates latent infections; secondly, we will evaluate the contribution of the toxins in B.
pseudomallei's ability to persist during host-associated in vivo conditions. Our proposal is significant because it
is expected to elucidate the role of the specific toxins that have a strong association with the persistence
phenotype, and this might result in the development of alternative therapeutic approaches to prevent latent
infections caused by B. pseudomallei, a CDC Category B Tier 1 Select Biothreat Agent and an understudied
emerging pathogen.

## Key facts

- **NIH application ID:** 10194359
- **Project number:** 5R21AI148913-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Alfredo G Torres
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2020-06-16 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194359

## Citation

> US National Institutes of Health, RePORTER application 10194359, Defining the role of toxin-antitoxin systems in persistence of Burkholderia pseudomallei (5R21AI148913-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194359. Licensed CC0.

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