# Antibiotic-induced virulence in Burkholderia pseudomallei

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2020 · $128,211

## Abstract

PROJECT SUMMARY 
The bacterium Burkholderia pseudomallei causes the human disease melioidosis and is currently the third 
leading cause of death in Northeast Thailand. Despite the increasing prevalence of melioidosis, mechanisms of 
B. pseudomallei pathogenesis remain poorly understood and treatment options are limited. This proposal is 
focused on a cytotoxic B. pseudomallei polyketide, malleilactone, which is important for B. pseudomallei 
pathogenesis in several infection models. Malleilactone is not produced in normal laboratory conditions, but its 
production can be elicited by certain antibiotics such as trimethoprim. Some of the antibiotics that induce 
malleilactone production are among the few available options to treat melioidosis. Our long-term goal is to 
define the underlying mechanisms of B. pseudomallei virulence, and use this information to identify novel 
therapeutic interventions to treat this challenging human disease. Here we propose to (i) synthesize and 
determine the mode of action of malleilactone, (ii) determine the spatial and temporal pattern of malleilactone 
expression and cytotoxicity in a murine model of melioidosis, and (iii) elucidate the regulatory pathway that 
triggers induction of the malleilactone biosynthetic genes using both directed and global approaches. These 
results are essential to gain a mechanistic understanding of how malleilactone increases B. pseudomallei 
pathogenesis and will provide insight into how this versatile pathogen has evolved the ability to adapt to 
different environments. In addition toxic polyketides are emerging as a broadly ubiquitous and poorly 
understood class of virulence factors in many pathogens, and we anticipate that B. pseudomallei and the 
robust animal models available for this species will provide insight into polyketide virulence mechanisms in a 
broader sense. Elucidating the underlying mechanisms that lead to malleilactone-dependent virulence will 
provide critical new information on B. pseudomallei pathogenesic mechanisms, and is an important step 
towards improving the currently limited treatment options for this devastating disease.

## Key facts

- **NIH application ID:** 9994336
- **Project number:** 5P20GM103638-09
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Josephine R Chandler
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $128,211
- **Award type:** 5
- **Project period:** 2017-07-15 → 2018-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994336

## Citation

> US National Institutes of Health, RePORTER application 9994336, Antibiotic-induced virulence in Burkholderia pseudomallei (5P20GM103638-09). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/9994336. Licensed CC0.

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