Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity.


Müller, CM; Conejero, L; Spink, N; Wand, ME; Bancroft, GJ; Titball, RW; (2012) Role of RelA and SpoT in Burkholderia pseudomallei Virulence and Immunity. Infection and immunity, 80 (9). pp. 3247-55. ISSN 0019-9567 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 ?relA ?spoT 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 ?relA ?spoT 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 ?relA ?spoT mutant may be a promising live-attenuated vaccine candidate.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 22778096
Web of Science ID: 307869100026
URI: http://researchonline.lshtm.ac.uk/id/eprint/208591

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