A putative p-type ATPase required for virulence and resistance to haem toxicity in Listeria monocytogenes

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dc.contributor.authorMcLaughlin, Heather P.
dc.contributor.authorXiao, Qiaobin
dc.contributor.authorRea, Rosemarie B.
dc.contributor.authorPi, Hualiang
dc.contributor.authorCasey, Pat G.
dc.contributor.authorDarby, Trevor
dc.contributor.authorCharbit, Alain
dc.contributor.authorSleator, Roy D.
dc.contributor.authorJoyce, Susan A.
dc.contributor.authorCowart, Richard E.
dc.contributor.authorHill, Colin
dc.contributor.authorKlebba, Phillip E.
dc.contributor.authorGahan, Cormac G.
dc.contributor.editorCornelis, Pierre
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Council for Science, Engineering and Technologyen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderNational Science Foundationen
dc.date.accessioned2012-12-10T13:38:16Z
dc.date.available2012-12-10T13:38:16Z
dc.date.copyright2012
dc.date.issued2012-02-21
dc.description.abstractRegulation of iron homeostasis in many pathogens is principally mediated by the ferric uptake regulator, Fur. Since acquisition of iron from the host is essential for the intracellular pathogen Listeria monocytogenes, we predicted the existence of Fur-regulated systems that support infection. We examined the contribution of nine Fur-regulated loci to the pathogenicity of L. monocytogenes in a murine model of infection. While mutating the majority of the genes failed to affect virulence, three mutants exhibited a significantly compromised virulence potential. Most striking was the role of the membrane protein we designate FrvA (Fur regulated virulence factor A; encoded by frvA [lmo0641]), which is absolutely required for the systemic phase of infection in mice and also for virulence in an alternative infection model, the Wax Moth Galleria mellonella. Further analysis of the DfrvA mutant revealed poor growth in iron deficient media and inhibition of growth by micromolar concentrations of haem or haemoglobin, a phenotype which may contribute to the attenuated growth of this mutant during infection. Uptake studies indicated that the DfrvA mutant is unaffected in the uptake of ferric citrate but demonstrates a significant increase in uptake of haem and haemin. The data suggest a potential role for FrvA as a haem exporter that functions, at least in part, to protect the cell against the potential toxicity of free haem.en
dc.description.sponsorshipScience Foundation Ireland (SFI-CSET); Irish Research Council for Science Engineering and Technology (Embark postgraduate scholarship programme (IRCSET ID1773)); National Institutes of Health, United States (Grant GM53836); National Science Foundation, United States (Grant MCB0417694)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMcLaughlin HP, Xiao Q, Rea RB, Pi H, Casey PG, et al. (2012) A Putative P-Type ATPase Required for Virulence and Resistance to Haem Toxicity in Listeria monocytogenes. PLoS ONE 7(2): e30928. doi:10.1371/journal.pone.0030928en
dc.identifier.doi10.1371/journal.pone.0030928
dc.identifier.endpagen/aen
dc.identifier.issn1932-6203
dc.identifier.issued2en
dc.identifier.journaltitlePLoS ONEen
dc.identifier.startpagen/aen
dc.identifier.urihttps://hdl.handle.net/10468/840
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030928
dc.rightsCopyright: © 2012 McLaughlin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.subjectHaem toxicityen
dc.subjectListeria monocytogenesen
dc.subjectFur (Ferric Uptake Regulator)en
dc.subjectVirulenceen
dc.subjectWax moth Galleria mellonellaen
dc.subjectFrvAen
dc.titleA putative p-type ATPase required for virulence and resistance to haem toxicity in Listeria monocytogenesen
dc.typeArticle (peer-reviewed)en
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