Show simple item record

dc.contributor.authorMüller, CM
dc.contributor.authorConejero, L
dc.contributor.authorSpink, N
dc.contributor.authorWand, ME
dc.contributor.authorBancroft, Gregory J.
dc.contributor.authorTitball, Richard W.
dc.date.accessioned2014-09-01T08:32:44Z
dc.date.issued2012-09
dc.description.abstractBurkholderia 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.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.identifier.citationVol. 80, Issue 9, pp. 3247 - 3255en_GB
dc.identifier.doi10.1128/IAI.00178-12
dc.identifier.grantnumberWT085162AIAen_GB
dc.identifier.otherIAI.00178-12
dc.identifier.urihttp://hdl.handle.net/10871/15416
dc.language.isoenen_GB
dc.publisherAmerican Society for Microbiologyen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/22778096en_GB
dc.relation.urlhttp://iai.asm.org/content/80/9/3247.longen_GB
dc.subjectAnimalsen_GB
dc.subjectBacterial Vaccinesen_GB
dc.subjectBurkholderia pseudomalleien_GB
dc.subjectDisease Models, Animalen_GB
dc.subjectFemaleen_GB
dc.subjectGene Deletionen_GB
dc.subjectHumansen_GB
dc.subjectLepidopteraen_GB
dc.subjectLigasesen_GB
dc.subjectMacrophagesen_GB
dc.subjectMelioidosisen_GB
dc.subjectMiceen_GB
dc.subjectMice, Inbred C57BLen_GB
dc.subjectMicrobial Viabilityen_GB
dc.subjectPyrophosphatasesen_GB
dc.subjectSurvival Analysisen_GB
dc.subjectVaccines, Attenuateden_GB
dc.subjectVirulenceen_GB
dc.subjectVirulence Factorsen_GB
dc.titleRole of RelA and SpoT in Burkholderia pseudomallei virulence and immunityen_GB
dc.typeArticleen_GB
dc.date.available2014-09-01T08:32:44Z
exeter.place-of-publicationUnited States
dc.descriptionnotes: PMCID: PMC3418737en_GB
dc.descriptionCopyright © 2012, American Society for Microbiology. All Rights Reserved. The authors have paid a fee to allow immediate free access to this article.en_GB
dc.descriptionThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.en_GB
dc.identifier.journalInfection and Immunityen_GB


Files in this item

This item appears in the following Collection(s)

Show simple item record