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

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dc.contributor.author McLaughlin, Heather P.
dc.contributor.author Xiao, Qiaobin
dc.contributor.author Rea, Rosemarie B.
dc.contributor.author Pi, Hualiang
dc.contributor.author Casey, Pat G.
dc.contributor.author Darby, Trevor
dc.contributor.author Charbit, Alain
dc.contributor.author Sleator, Roy D.
dc.contributor.author Joyce, Susan A.
dc.contributor.author Cowart, Richard E.
dc.contributor.author Hill, Colin
dc.contributor.author Klebba, Phillip E.
dc.contributor.author Gahan, Cormac G.
dc.contributor.editor Cornelis, Pierre
dc.date.accessioned 2012-12-10T13:38:16Z
dc.date.available 2012-12-10T13:38:16Z
dc.date.copyright 2012
dc.date.issued 2012-02-21
dc.identifier.citation McLaughlin 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.0030928 en
dc.identifier.volume 7 en
dc.identifier.issued 2 en
dc.identifier.startpage n/a en
dc.identifier.endpage n/a en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/840
dc.identifier.doi 10.1371/journal.pone.0030928
dc.description.abstract Regulation 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.sponsorship Science 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher PLOS en
dc.relation.uri http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030928
dc.rights Copyright: © 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.uri http://creativecommons.org/licenses/by/2.5/ en
dc.subject Haem toxicity en
dc.subject Listeria monocytogenes en
dc.subject Fur (Ferric Uptake Regulator) en
dc.subject Virulence en
dc.subject Wax moth Galleria mellonella en
dc.subject FrvA en
dc.title A putative p-type ATPase required for virulence and resistance to haem toxicity in Listeria monocytogenes en
dc.type Article (peer-reviewed) en
dc.internal.authorurl http://publish.ucc.ie/researchprofiles/D010/chill en
dc.internal.authorcontactother Colin Hill, Department of Microbiology, University College Cork, Ireland. Email: c.hill@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 146554532 en
dc.internal.rssid 424083775
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council for Science, Engineering and Technology en
dc.contributor.funder National Institutes of Health en
dc.contributor.funder National Science Foundation en
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLoS ONE en
dc.internal.copyrightchecked Sherpa Roemeo Green Journal. Policy: The Public Library of Science (PLOS) applies the Creative Commons Attribution License (CC-BY) to works we publish (read the human-readable summary or the full license legal code). Under this license, authors retain ownership of the copyright for their content, but allow anyone to download, reuse, reprint, modify, distribute, and/or copy the content as long as the original authors and source are cited. No permission is required from the authors or the publishers. Appropriate attribution can be provided by simply citing the original article (e.g., Kaltenbach LS et al. (2007) Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLOS Genet 3(5): e82. doi:10.1371/journal.pgen.0030082). For any reuse or redistribution of a work, users must also make clear the license terms under which the work was published. en
dc.internal.IRISemailaddress c.hill@ucc.ie en
dc.internal.IRISemailaddress s.joyce@ucc.ie en


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Copyright: © 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. Except where otherwise noted, this item's license is described as Copyright: © 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.
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