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dc.contributor.authorHorton, Rachel E
dc.contributor.authorGrant, Gary D
dc.contributor.authorMatthews, Ben
dc.contributor.authorBatzloff, Michael
dc.contributor.authorOwen, Suzzanne J
dc.contributor.authorKyan, Stephanie
dc.contributor.authorFlegg, Cameron P
dc.contributor.authorClark, Amanda M
dc.contributor.authorUlett, Glen C
dc.contributor.authorMorrison, Nigel
dc.contributor.authorPeak, Ian R
dc.contributor.authorBeacham, Ifor R
dc.date.accessioned2017-05-03T12:19:15Z
dc.date.available2017-05-03T12:19:15Z
dc.date.issued2013
dc.date.modified2013-12-03T00:21:54Z
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0063394
dc.identifier.urihttp://hdl.handle.net/10072/54760
dc.description.abstractBurkholderia pseudomallei is a Gram-negative environmental bacterium and the causative agent of melioidosis, a potentially fatal, acute or chronic disease endemic in the tropics. Acyl homoserine lactone (AHL)-mediated quorum sensing and signalling have been associated with virulence and biofilm formation in numerous bacterial pathogens. In the canonical acyl-homoserine lactone signalling paradigm, AHLs are detected by a response regulator. B. pseudomallei encodes three AHL synthases, encoded by bpsI1, bpsI2 and bpsI3, and five regulator genes. In this study, we mutated the B. pseudomallei AHL synthases individually and in double and triple combination. Five AHLs were detected and quantified by tandem liquid chromatography-mass spectroscopy. The major AHLs produced were N-octanoylhomoserine lactone and N-(3-hydroxy- decanoyl)homoserine lactone, the expression of which depended on bpsI1 and bpsI2, respectively. B. pseudomallei infection of macrophage cells causes cell fusion, leading to multinucleated cells (3 or more nuclei per cell). A triple mutant defective in production of all three AHL synthases was associated with a striking phenotype of massively enhanced host cellular fusion in macrophages. However, neither abrogation of host cell fusion, achieved by mutation of bimA or hcp1, nor enhancement of fusion altered intracellular replication of B. pseudomallei. Furthermore, when tested in murine models of acute melioidosis the AHL synthase mutants were not attenuated for virulence. Collectively, this study identifies important new aspects of the genetic basis of AHL synthesis in B. pseudomallei and the roles of these AHLs in systemic infection and in cell fusion in macrophages for this important human pathogen.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1716187 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome63394-1
dc.relation.ispartofpagetoe63394-9
dc.relation.ispartofissue5
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume8
dc.rights.retentionY
dc.subject.fieldofresearchInfectious agents
dc.subject.fieldofresearchcode310702
dc.titleQuorum Sensing Negatively Regulates Multinucleate Cell Formation during Intracellular Growth of Burkholderia pseudomallei in Macrophage-Like Cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://www.plos.org/journals/license.html
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2013 Horton et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
gro.date.issued2013
gro.hasfulltextFull Text
gro.griffith.authorBeacham, Ifor R.
gro.griffith.authorMorrison, Nigel A.
gro.griffith.authorPeak, Ian
gro.griffith.authorOwen, Suzzanne J.
gro.griffith.authorGrant, Gary D.
gro.griffith.authorUlett, Glen C.


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