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Microbial Immunity and Vaccines

Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity

Claudia M. Müller, Laura Conejero, Natasha Spink, Matthew E. Wand, Gregory J. Bancroft, Richard W. Titball
A. Camilli, Editor
Claudia M. Müller
aCollege of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom
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Laura Conejero
bLondon School of Hygiene and Tropical Medicine, London, United Kingdom
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Natasha Spink
bLondon School of Hygiene and Tropical Medicine, London, United Kingdom
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Matthew E. Wand
aCollege of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom
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Gregory J. Bancroft
bLondon School of Hygiene and Tropical Medicine, London, United Kingdom
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Richard W. Titball
aCollege of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter, Devon, United Kingdom
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A. Camilli
Roles: Editor
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DOI: 10.1128/IAI.00178-12
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ABSTRACT

Burkholderia pseudomallei is a Gram-negative soil bacterium and the causative agent of melioidosis, a disease of humans and animals. It is also listed as a category B bioterrorism threat agent by the U.S. Centers for Disease Control and Prevention, and there is currently no melioidosis vaccine available. Small modified nucleotides such as the hyperphosphorylated guanosine molecules ppGpp and pppGpp play an important role as signaling molecules in prokaryotes. They mediate a global stress response under starvation conditions and have been implicated in the regulation of virulence and survival factors in many bacterial species. In this study, we created a relA spoT double mutant in B. pseudomallei strain K96243, which lacks (p)ppGpp-synthesizing enzymes, and investigated its phenotype in vitro and in vivo. The B. pseudomallei ΔrelA ΔspoT mutant displayed a defect in stationary-phase survival and intracellular replication in murine macrophages. Moreover, the mutant was attenuated in the Galleria mellonella insect model and in both acute and chronic mouse models of melioidosis. Vaccination of mice with the ΔrelA ΔspoT mutant resulted in partial protection against infection with wild-type B. pseudomallei. In summary, (p)ppGpp signaling appears to represent an essential component of the regulatory network governing virulence gene expression and stress adaptation in B. pseudomallei, and the ΔrelA ΔspoT mutant may be a promising live-attenuated vaccine candidate.

  • Copyright © 2012, American Society for Microbiology. All Rights Reserved.

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Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity
Claudia M. Müller, Laura Conejero, Natasha Spink, Matthew E. Wand, Gregory J. Bancroft, Richard W. Titball
Infection and Immunity Aug 2012, 80 (9) 3247-3255; DOI: 10.1128/IAI.00178-12

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Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity
Claudia M. Müller, Laura Conejero, Natasha Spink, Matthew E. Wand, Gregory J. Bancroft, Richard W. Titball
Infection and Immunity Aug 2012, 80 (9) 3247-3255; DOI: 10.1128/IAI.00178-12
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