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<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">RegR, a Global LacI/GalR Family Regulator, Modulates Virulence and Competence in
<italic>Streptococcus pneumoniae</italic>
</title>
<author>
<name sortKey="Chapuy Regaud, Sabine" sort="Chapuy Regaud, Sabine" uniqKey="Chapuy Regaud S" first="Sabine" last="Chapuy-Regaud">Sabine Chapuy-Regaud</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ogunniyi, A David" sort="Ogunniyi, A David" uniqKey="Ogunniyi A" first="A. David" last="Ogunniyi">A. David Ogunniyi</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Diallo, Nicole" sort="Diallo, Nicole" uniqKey="Diallo N" first="Nicole" last="Diallo">Nicole Diallo</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huet, Yvette" sort="Huet, Yvette" uniqKey="Huet Y" first="Yvette" last="Huet">Yvette Huet</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Desnottes, Jean Francois" sort="Desnottes, Jean Francois" uniqKey="Desnottes J" first="Jean-François" last="Desnottes">Jean-François Desnottes</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Paton, James C" sort="Paton, James C" uniqKey="Paton J" first="James C." last="Paton">James C. Paton</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Escaich, Sonia" sort="Escaich, Sonia" uniqKey="Escaich S" first="Sonia" last="Escaich">Sonia Escaich</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Trombe, Marie Claude" sort="Trombe, Marie Claude" uniqKey="Trombe M" first="Marie-Claude" last="Trombe">Marie-Claude Trombe</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">12704136</idno>
<idno type="pmc">153264</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC153264</idno>
<idno type="RBID">PMC:153264</idno>
<idno type="doi">10.1128/IAI.71.5.2615-2625.2003</idno>
<date when="2003">2003</date>
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<analytic>
<title xml:lang="en" level="a" type="main">RegR, a Global LacI/GalR Family Regulator, Modulates Virulence and Competence in
<italic>Streptococcus pneumoniae</italic>
</title>
<author>
<name sortKey="Chapuy Regaud, Sabine" sort="Chapuy Regaud, Sabine" uniqKey="Chapuy Regaud S" first="Sabine" last="Chapuy-Regaud">Sabine Chapuy-Regaud</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ogunniyi, A David" sort="Ogunniyi, A David" uniqKey="Ogunniyi A" first="A. David" last="Ogunniyi">A. David Ogunniyi</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Diallo, Nicole" sort="Diallo, Nicole" uniqKey="Diallo N" first="Nicole" last="Diallo">Nicole Diallo</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Huet, Yvette" sort="Huet, Yvette" uniqKey="Huet Y" first="Yvette" last="Huet">Yvette Huet</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Desnottes, Jean Francois" sort="Desnottes, Jean Francois" uniqKey="Desnottes J" first="Jean-François" last="Desnottes">Jean-François Desnottes</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Paton, James C" sort="Paton, James C" uniqKey="Paton J" first="James C." last="Paton">James C. Paton</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Escaich, Sonia" sort="Escaich, Sonia" uniqKey="Escaich S" first="Sonia" last="Escaich">Sonia Escaich</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Trombe, Marie Claude" sort="Trombe, Marie Claude" uniqKey="Trombe M" first="Marie-Claude" last="Trombe">Marie-Claude Trombe</name>
<affiliation>
<nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Infection and Immunity</title>
<idno type="ISSN">0019-9567</idno>
<idno type="eISSN">1098-5522</idno>
<imprint>
<date when="2003">2003</date>
</imprint>
</series>
</biblStruct>
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<front>
<div type="abstract" xml:lang="en">
<p>The homolactic and catalase-deficient pathogen
<italic>Streptococcus pneumoniae</italic>
is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation. In this work, we show that the global regulator RegR is also involved in these traits. Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase. In bacteria grown in vitro, RegR represses hyaluronidase. At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence. These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization. Although the RegR
<sub>0</sub>
(where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional
<italic>hyl
<sub>0</sub>
</italic>
(where 0 indicates the loss of function) mutation in the RegR
<sub>0</sub>
strain 23302 dramatically reduces its virulence. This indicates that residual virulence of the RegR
<sub>0</sub>
Hyl
<sup>+</sup>
derivative is due to hyaluronidase and supports the dual role of RegR in virulence. This LacI/GalR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Infect Immun</journal-id>
<journal-id journal-id-type="publisher-id">iai</journal-id>
<journal-title>Infection and Immunity</journal-title>
<issn pub-type="ppub">0019-9567</issn>
<issn pub-type="epub">1098-5522</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">12704136</article-id>
<article-id pub-id-type="pmc">153264</article-id>
<article-id pub-id-type="publisher-id">1538</article-id>
<article-id pub-id-type="doi">10.1128/IAI.71.5.2615-2625.2003</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Molecular Pathogenesis</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>RegR, a Global LacI/GalR Family Regulator, Modulates Virulence and Competence in
<italic>Streptococcus pneumoniae</italic>
</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Chapuy-Regaud</surname>
<given-names>Sabine</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ogunniyi</surname>
<given-names>A. David</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Diallo</surname>
<given-names>Nicole</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Huet</surname>
<given-names>Yvette</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Desnottes</surname>
<given-names>Jean-François</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Paton</surname>
<given-names>James C.</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Escaich</surname>
<given-names>Sonia</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Trombe</surname>
<given-names>Marie-Claude</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">Laboratoire “Interactions et Signalisation Cellulaire: Relation Hôte Pathogène,” Institut Louis Bugnard, Centre Hospitalo-Universitaire de Rangueil, Université Paul Sabatier, 31403 Toulouse Cedex,
<label>1</label>
Aventis Pharma, 94403 Vitry sur Seine,
<label>3</label>
Mutabilis SA, Faculté de Médecine Necker, 75730 Paris Cedex 15, France,
<label>4</label>
Department of Molecular Biosciences, Adelaide University, Adelaide, South Australia 5005, Australia
<label>2</label>
</aff>
<author-notes>
<fn id="cor1">
<label>*</label>
<p>Corresponding author. Mailing address: Lab. Interactions et Signalisation cellulaire: Relation hôte pathogene, EA3036, IFR31 Inst. Louis Bugnard, Centre Hospitalo-Univ. de Rangueil, Université Paul Sabatier, 31403 Toulouse Cedex, France. Phone: 33 (0)5 61 32 29 74. Fax: 33 (0)5 61 32 26 20. E-mail:
<email>trombe@cict.fr</email>
.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>5</month>
<year>2003</year>
</pub-date>
<volume>71</volume>
<issue>5</issue>
<fpage>2615</fpage>
<lpage>2625</lpage>
<history>
<date date-type="received">
<day>22</day>
<month>10</month>
<year>2002</year>
</date>
<date date-type="rev-recd">
<day>27</day>
<month>1</month>
<year>2003</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>2</month>
<year>2003</year>
</date>
</history>
<copyright-statement>Copyright © 2003, American Society for Microbiology</copyright-statement>
<copyright-year>2003</copyright-year>
<abstract>
<p>The homolactic and catalase-deficient pathogen
<italic>Streptococcus pneumoniae</italic>
is not only tolerant to oxygen but requires the activity of its NADH oxidase, Nox, to develop optimal virulence and competence for genetic transformation. In this work, we show that the global regulator RegR is also involved in these traits. Genetic dissection revealed that RegR regulates competence and the expression of virulence factors, including hyaluronidase. In bacteria grown in vitro, RegR represses hyaluronidase. At neutral pH, it increases adherence to A549 epithelial cells, and at alkaline pH, it acts upstream of the CiaRH two-component signaling system to activate competence. These phenotypes are not associated with changes in antibiotic resistance, central metabolism, and carbohydrate utilization. Although the RegR
<sub>0</sub>
(where 0 indicates the loss of the protein) mutation is sufficient to attenuate experimental virulence of strain 23477 in mice, the introduction of an additional
<italic>hyl
<sub>0</sub>
</italic>
(where 0 indicates the loss of function) mutation in the RegR
<sub>0</sub>
strain 23302 dramatically reduces its virulence. This indicates that residual virulence of the RegR
<sub>0</sub>
Hyl
<sup>+</sup>
derivative is due to hyaluronidase and supports the dual role of RegR in virulence. This LacI/GalR regulator, not essential for in vitro growth in rich media, is indeed involved in the adaptive response of the pneumococcus via its control of competence, adherence, and virulence.</p>
</abstract>
</article-meta>
<notes>
<fn-group>
<fn>
<p>
<italic>Editor:</italic>
A. D. O'Brien</p>
</fn>
</fn-group>
</notes>
</front>
</pmc>
</record>

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