Dose‐dependant acute or subacute disease caused byBurkholderia pseudomalleistrain NCTC 13392 in a BALB/c aerosol model of infection

Abstract

Aims The goal of this study was to examine, for the first time, the virulence and pathogenicity of aerosolized Burkholderia pseudomallei, strain NCTC 13392, in BALB/c mice in order to develop an animal model for testing novel medical countermeasures (MCMs) for the treatment of human acute and subacute (a disease state between acute and chronic) melioidosis. Methods and Results BALB/c mice were exposed to varying doses of aerosolized bacteria. Acute disease was seen in animals exposed to a very‐high dose (≥103 CFU per animal) and death occurred 3–4 days postchallenge (pc). Bacteria were detected in the lungs, liver, kidney and spleen. In contrast, animals exposed to a low dose (<10 CFU per animal) survived to the end of the study (day 30 pc) but developed weight loss, a bacterial tissue burden and increasing clinical signs of infection from day 20 pc onwards, mimicking a subacute form of the disease. Pathological changes in the tissues mirrored these findings. Conclusions This proof of concept study has shown that B. pseudomallei strain NCTC 13392 is virulent and pathogenic in BALB/c mice, when delivered by aerosol. By varying the doses of aerosolized bacteria it was possible to mimic characteristics of both human acute and subacute melioidosis, at the same time, within the same study. Significance and Impact of the Study Burkholderia pseudomallei, the aetiological agent of melioidosis, causes a serious and often fatal disease in humans and animals. Novel MCMs are urgently needed for both public health and biodefense purposes. The present model provides a useful tool for the assessment and evaluation of new MCMs (e.g. therapeutics and vaccines) and offers the potential for testing new treatments for both subacute to chronic and acute melioidosis prior to human clinical trials.

Evaluation of four sampling devices for Burkholderia pseudomallei laboratory aerosol studies

“…The suspension containing stationary phase bacteria was diluted 1:10 in LB broth or LB broth supplemented with 4% glycerol (LB4G) and stored at room temperature for up to two hours until use. Both LB broth and LB4G, or media with similar compositions, are commonly used for culturing B. pseudomallei for aerosol experiments [27,[37][38][39][40][41]. In the present study, aerosol starting material suspensions in LB had a mean titer of 8.69 ± 0.08 Log colony forming units (CFU)/mL, and suspensions in LB4G had a mean titer of 8.71 ± 0.08 Log CFU/mL.…”

The BALB/c Mouse Model for the Evaluation of Therapies to Treat Infections with Aerosolized Burkholderia pseudomallei

“…A target dose of approximately 20–50 LD 50 equivalents achieves an acute, lethal infection. Lower LD 50 challenges can lead to a chronic infection with a prolonged time to death (weeks) [ 24 ].…”