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Published on: October 15, 2013
Neurotropic threat characterization of Burkholderia pseudomallei strains
Abstract:
The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989-October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.
Insights
Certain Burkholderia pseudomallei strains, not specific patient diagnoses, drive severe neurologic melioidosis. These virulent strains rapidly spread to multiple organs, including the central nervous system, regardless of infection route.
Area of Science:
- Infectious Diseases
- Microbiology
- Neuroscience
Background:
- Neurologic melioidosis has a high mortality rate.
- The specific Burkholderia pseudomallei strains and infection routes that lead to central nervous system involvement are not well understood.
Purpose of the Study:
- To investigate whether particular B. pseudomallei strains are more prone to causing central nervous system infections.
- To determine if the route of infection impacts the neurotropic potential of B. pseudomallei.
Main Methods:
- Comparison of virulence and dissemination of Australian clinical B. pseudomallei isolates.
- Intranasal and subcutaneous infection models in mice.
- Isolates were obtained from patients with neurologic and nonneurologic melioidosis (October 1989–October 2012).
Main Results:
- Neurotropism was not a unique characteristic of B. pseudomallei isolates from neurologic melioidosis patients.
- A specific subset of B. pseudomallei strains demonstrated heightened potential for rapid dissemination to multiple tissues, including the CNS.
- This dissemination occurred irrespective of the initial infection route (intranasal or subcutaneous).
Conclusions:
- The pathogenic potential for severe melioidosis, including CNS invasion, is linked to specific B. pseudomallei strains rather than the clinical presentation of the initial infection.
- These findings have significant public health implications for early and appropriate treatment strategies following exposure to invasive B. pseudomallei.
- Further research into B. pseudomallei pathology can reduce morbidity and mortality associated with this disease.
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