Divergent evolution of the activity and regulation of the glutamate decarboxylase systems in Listeria monocytogenes EGD-e and 10403S: roles in virulence and acid tolerance

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dc.contributor.authorFeehily, Conor
dc.contributor.authorFinnerty, Aiden
dc.contributor.authorCasey, Pat G.
dc.contributor.authorHill, Colin
dc.contributor.authorGahan, Cormac G.en
dc.contributor.authorO'Byrne, Conor P.
dc.contributor.authorKaratzas, Kimon-Andreas G.
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderEuropean Commission
dc.contributor.funderNational University of Ireland Galway
dc.date.accessioned2016-02-17T11:43:38Z
dc.date.available2016-02-17T11:43:38Z
dc.date.issued2014-01-01
dc.description.abstractThe glutamate decarboxylase (GAD) system has been shown to be important for the survival of Listeria monocytogenes in low pH environments. The bacterium can use this faculty to maintain pH homeostasis under acidic conditions. The accepted model for the GAD system proposes that the antiport of glutamate into the bacterial cell in exchange for c-aminobutyric acid (GABA) is coupled to an intracellular decarboxylation reaction of glutamate into GABA that consumes protons and therefore facilitates pH homeostasis. Most strains of L. monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a glutamate decarboxylase dedicated to the intracellular GAD system (GAD(i)), which produces GABA from cytoplasmic glutamate in the absence of antiport activity. We also compare the functionality of the GAD system between two commonly studied reference strains, EGD-e and 10403S with differences in terms of acid resistance. Through functional genomics we show that EGD-e is unable to export GABA and relies exclusively in the GADi system, which is driven primarily by GadD3 in this strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular and extracellular GAD system (GAD(i)/GAD(e)). Through experiments with a murinised variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant role in the overall virulence of this strain. Double mutants lacking either gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were significantly affected in their ability to cause infection following oral inoculation. Since EGDm exploits GAD(i) but not GAD(e) the results indicate that the GAD(i) system makes a contribution to virulence within the mouse. Furthermore, we also provide evidence that there might be a separate line of evolution in the GAD system between two commonly used reference strains.en
dc.description.sponsorshipScience Foundation Ireland (Starting Investigator Research Grant 09/SIRG/B1570; SFI/12/RC/2273; 12/RC/2273); European Commission (Marie Curie European Reintegration Grant 265154)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide112649
dc.identifier.citationFeehily C, Finnerty A, Casey PG, Hill C, Gahan CGM, O'Byrne CP, et al. (2014) Divergent Evolution of the Activity and Regulation of the Glutamate Decarboxylase Systems in Listeria monocytogenes EGD-e and 10403S: Roles in Virulence and Acid Tolerance. PLoS ONE 9(11): e112649. doi:10.1371/journal.pone.0112649
dc.identifier.doi10.1371/journal.pone.0112649
dc.identifier.issn1932-6203
dc.identifier.issued11en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2321
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2015 Feehily 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 crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectOral infectionen
dc.subjectResistanceen
dc.subjectPhen
dc.subjectIdentificationen
dc.subjectExpressionen
dc.subjectStressen
dc.subjectGrowthen
dc.subjectGeneen
dc.subjectInhibitionen
dc.subjectSurvivalen
dc.subject~Microbiology - Journal Articles~en
dc.titleDivergent evolution of the activity and regulation of the glutamate decarboxylase systems in Listeria monocytogenes EGD-e and 10403S: roles in virulence and acid toleranceen
dc.typeArticle (peer-reviewed)en
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