Neurotropic threat characterization of Burkholderia pseudomallei strains.

Jodie Morris,Anne Fane,Bart J Currie,Catherine Rush,Natkunam Ketheesan,Mark Mayo,Brenda Govan

doi:10.3201/eid2101.131570

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.

Highlights

The death rate for neurologic melioidosis is high
Little is known about the potential for different B. pseudomallei strains to cause severe disease, including whether particular strains are more likely to cause neurologic sequelae or whether central nervous system (CNS) involvement is a consequence of the mode of delivery of B. pseudomallei
Initial suggestions that neurologic melioidosis might result from damage from immune or toxin-mediated mechanisms [6,12] has been supplanted by the recognition that direct invasion of brain and spinal cord by bacteria is evident on histologic examination of samples from case-patients who died [16]

Summary

Introduction

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. 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. Initial suggestions that neurologic melioidosis might result from damage from immune or toxin-mediated mechanisms [6,12] has been supplanted by the recognition that direct invasion of brain and spinal cord by bacteria is evident on histologic examination of samples from case-patients who died [16]. Given the high rate of death from neurologic melioidosis, interest is increasing in improving understanding of its pathogenesis, the potential for different B

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Conclusion