Related Experiment Video
Updated: Mar 26, 2026
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Attenuation of a select agent-excluded Burkholderia pseudomallei capsule mutant in hamsters
Maria G Gutierrez1, Jonathan M Warawa2
1Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, United States.
Abstract:
Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon. Given it is potential to cause a lethal respiratory disease, research with fully virulent B. pseudomallei is conducted in Biosafety Level 3 (BSL-3) laboratory spaces. The logistical, financial, and administrative burden of Tier 1 select agent BSL-3 research has created an interest in mitigating such burdens through the use of either attenuated B. pseudomallei strains at BSL-2, or research with surrogate species, such as Burkholderia thailandensis. Previously, attenuated B. pseudomallei auxotroph mutants (asd and purM) have been approved for exclusion from select agent requirements, allowing for in vitro studies to be conducted at BSL-2. Acapsular B. pseudomallei mutants are known to be strongly attenuated in a variety of animal models, and yet acapsular B. pseudomallei mutants do not require nutritional supplementation, and can be studied within cultured macrophages, performing phenotypically similarly to parent strains. We demonstrate that the loss of a 30.8 kb region of the wcb capsule operon allows for a dramatic >4.46 log attenuation in a hamster intraperitoneal infection model, and report that this strain, JW270, has met criteria for exclusion from select agent requirements.
Insights
Researchers developed an acapsular Burkholderia pseudomallei strain, JW270, significantly reducing its virulence. This attenuated strain meets criteria for exclusion from select agent requirements, simplifying BSL-3 research.
Area of Science:
- Microbiology
- Pathogen research
- Biosecurity
Background:
- Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon.
- Research with virulent strains necessitates Biosafety Level 3 (BSL-3) containment, imposing significant burdens.
- Attenuated strains or surrogates are sought to mitigate BSL-3 research requirements.
Purpose of the Study:
- To develop and characterize an attenuated Burkholderia pseudomallei strain for potential exclusion from select agent requirements.
- To assess the virulence of an acapsular mutant in a relevant animal model.
- To evaluate the feasibility of conducting research with less stringent biosafety levels.
Main Methods:
- Generation of an acapsular Burkholderia pseudomallei mutant by deleting a 30.8 kb region of the wcb capsule operon.
- Virulence assessment using a hamster intraperitoneal infection model.
- Evaluation of criteria for exclusion from select agent requirements.
Main Results:
- The acapsular mutant, JW270, demonstrated a >4.46 log attenuation in the hamster model.
- Acapsular mutants retain phenotypic similarity to parent strains and do not require nutritional supplementation.
- JW270 met the criteria for exclusion from select agent requirements.
Conclusions:
- Deletion of the wcb capsule operon region results in significant attenuation of Burkholderia pseudomallei.
- The acapsular strain JW270 offers a viable alternative for certain research applications, potentially reducing the need for BSL-3 containment.
- This finding facilitates safer and more accessible research on B. pseudomallei.
