Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in Liberibacter asiaticus
Identifieur interne : 000200 ( Pmc/Checkpoint ); précédent : 000199; suivant : 000201Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in Liberibacter asiaticus
Auteurs : Christopher L. Gardner ; Fernando A. Pagliai ; Lei Pan ; Lora Bojilova ; Maria I. Torino ; Graciela L. Lorca ; Claudio F. GonzalezSource :
- Frontiers in Microbiology [ 1664-302X ] ; 2016.
Abstract
CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein in
Url:
DOI: 10.3389/fmicb.2016.01630
PubMed: 27803694
PubMed Central: 5067538
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in <italic>Liberibacter asiaticus</italic></title><author><name sortKey="Gardner, Christopher L" sort="Gardner, Christopher L" uniqKey="Gardner C" first="Christopher L." last="Gardner">Christopher L. Gardner</name></author><author><name sortKey="Pagliai, Fernando A" sort="Pagliai, Fernando A" uniqKey="Pagliai F" first="Fernando A." last="Pagliai">Fernando A. Pagliai</name></author><author><name sortKey="Pan, Lei" sort="Pan, Lei" uniqKey="Pan L" first="Lei" last="Pan">Lei Pan</name></author><author><name sortKey="Bojilova, Lora" sort="Bojilova, Lora" uniqKey="Bojilova L" first="Lora" last="Bojilova">Lora Bojilova</name></author><author><name sortKey="Torino, Maria I" sort="Torino, Maria I" uniqKey="Torino M" first="Maria I." last="Torino">Maria I. Torino</name></author><author><name sortKey="Lorca, Graciela L" sort="Lorca, Graciela L" uniqKey="Lorca G" first="Graciela L." last="Lorca">Graciela L. Lorca</name></author><author><name sortKey="Gonzalez, Claudio F" sort="Gonzalez, Claudio F" uniqKey="Gonzalez C" first="Claudio F." last="Gonzalez">Claudio F. Gonzalez</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27803694</idno><idno type="pmc">5067538</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067538</idno><idno type="RBID">PMC:5067538</idno><idno type="doi">10.3389/fmicb.2016.01630</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000F11</idno><idno type="wicri:Area/Pmc/Curation">000F10</idno><idno type="wicri:Area/Pmc/Checkpoint">000200</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in <italic>Liberibacter asiaticus</italic></title><author><name sortKey="Gardner, Christopher L" sort="Gardner, Christopher L" uniqKey="Gardner C" first="Christopher L." last="Gardner">Christopher L. Gardner</name></author><author><name sortKey="Pagliai, Fernando A" sort="Pagliai, Fernando A" uniqKey="Pagliai F" first="Fernando A." last="Pagliai">Fernando A. Pagliai</name></author><author><name sortKey="Pan, Lei" sort="Pan, Lei" uniqKey="Pan L" first="Lei" last="Pan">Lei Pan</name></author><author><name sortKey="Bojilova, Lora" sort="Bojilova, Lora" uniqKey="Bojilova L" first="Lora" last="Bojilova">Lora Bojilova</name></author><author><name sortKey="Torino, Maria I" sort="Torino, Maria I" uniqKey="Torino M" first="Maria I." last="Torino">Maria I. Torino</name></author><author><name sortKey="Lorca, Graciela L" sort="Lorca, Graciela L" uniqKey="Lorca G" first="Graciela L." last="Lorca">Graciela L. Lorca</name></author><author><name sortKey="Gonzalez, Claudio F" sort="Gonzalez, Claudio F" uniqKey="Gonzalez C" first="Claudio F." last="Gonzalez">Claudio F. Gonzalez</name></author></analytic><series><title level="j">Frontiers in Microbiology</title><idno type="eISSN">1664-302X</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein in <italic>Liberibacter asiaticus</italic>. PrbP was found to regulate expression of a small subset of ribosomal genes through interactions with the β-subunit of the RNA polymerase and a short, specific sequence on the promoter region. Molecular screening assays were performed to identify small molecules that interact with PrbP <italic>in vitro</italic>. Chemical hits were analyzed for therapeutic efficacy against <italic>L. asiaticus</italic> via an infected leaf assay, where the transcriptional activity of <italic>L. asiaticus</italic> was found to decrease significantly after exposure to tolfenamic acid. Similarly, tolfenamic acid was found to inhibit <italic>L. asiaticus</italic> infection in highly symptomatic citrus seedlings. Our results indicate that PrbP is an important transcriptional regulator for survival of <italic>L. asiaticus in planta</italic>, and the chemicals identified by molecular screening assays could be used as a therapeutic treatment for huanglongbing disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aritua, V" uniqKey="Aritua V">V. Aritua</name></author><author><name sortKey="Achor, D" uniqKey="Achor D">D. Achor</name></author><author><name sortKey="Gmitter, F G" uniqKey="Gmitter F">F. G. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Microbiol</journal-id><journal-id journal-id-type="iso-abbrev">Front Microbiol</journal-id><journal-id journal-id-type="publisher-id">Front. Microbiol.</journal-id><journal-title-group><journal-title>Frontiers in Microbiology</journal-title></journal-title-group><issn pub-type="epub">1664-302X</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27803694</article-id><article-id pub-id-type="pmc">5067538</article-id><article-id pub-id-type="doi">10.3389/fmicb.2016.01630</article-id><article-categories><subj-group subj-group-type="heading"><subject>Microbiology</subject><subj-group><subject>Original Research</subject></subj-group></subj-group></article-categories><title-group><article-title>Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in <italic>Liberibacter asiaticus</italic></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gardner</surname><given-names>Christopher L.</given-names></name><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/238518/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Pagliai</surname><given-names>Fernando A.</given-names></name><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/272725/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Pan</surname><given-names>Lei</given-names></name><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/366985/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Bojilova</surname><given-names>Lora</given-names></name><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/384208/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Torino</surname><given-names>Maria I.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Lorca</surname><given-names>Graciela L.</given-names></name><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/255237/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Gonzalez</surname><given-names>Claudio F.</given-names></name><xref ref-type="author-notes" rid="fn002"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://loop.frontiersin.org/people/238178/overview"></uri></contrib></contrib-group><aff><institution>Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida</institution><country>Gainesville, FL, USA</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Abelardo Margolles, Spanish National Research Council, Spain</p></fn><fn fn-type="edited-by"><p>Reviewed by: Vishvanath Tiwari, Central University of Rajasthan, India; Hongxia Wang, University of Alabama at Birmingham, USA</p></fn><corresp id="fn001">*Correspondence: Graciela L. Lorca <email xlink:type="simple">glorca@ufl.edu</email></corresp><corresp id="fn002">Claudio F. Gonzalez <email xlink:type="simple">cfgonzalez@ufl.edu</email></corresp><fn fn-type="other" id="fn003"><p>This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology</p></fn></author-notes><pub-date pub-type="epub"><day>18</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>7</volume><elocation-id>1630</elocation-id><history><date date-type="received"><day>03</day><month>8</month><year>2016</year></date><date date-type="accepted"><day>30</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016 Gardner, Pagliai, Pan, Bojilova, Torino, Lorca and Gonzalez.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Gardner, Pagliai, Pan, Bojilova, Torino, Lorca and Gonzalez</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein in <italic>Liberibacter asiaticus</italic>. PrbP was found to regulate expression of a small subset of ribosomal genes through interactions with the β-subunit of the RNA polymerase and a short, specific sequence on the promoter region. Molecular screening assays were performed to identify small molecules that interact with PrbP <italic>in vitro</italic>. Chemical hits were analyzed for therapeutic efficacy against <italic>L. asiaticus</italic> via an infected leaf assay, where the transcriptional activity of <italic>L. asiaticus</italic> was found to decrease significantly after exposure to tolfenamic acid. Similarly, tolfenamic acid was found to inhibit <italic>L. asiaticus</italic> infection in highly symptomatic citrus seedlings. Our results indicate that PrbP is an important transcriptional regulator for survival of <italic>L. asiaticus in planta</italic>, and the chemicals identified by molecular screening assays could be used as a therapeutic treatment for huanglongbing disease.</p></abstract><kwd-group><kwd>transcriptional accessory protein</kwd><kwd><italic>Liberibacter asiaticus</italic></kwd><kwd>tolfenamic acid</kwd><kwd>antimicrobial</kwd><kwd>citrus</kwd></kwd-group><counts><fig-count count="10"></fig-count><table-count count="3"></table-count><equation-count count="0"></equation-count><ref-count count="30"></ref-count><page-count count="16"></page-count><word-count count="8561"></word-count></counts></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Bojilova, Lora" sort="Bojilova, Lora" uniqKey="Bojilova L" first="Lora" last="Bojilova">Lora Bojilova</name><name sortKey="Gardner, Christopher L" sort="Gardner, Christopher L" uniqKey="Gardner C" first="Christopher L." last="Gardner">Christopher L. Gardner</name><name sortKey="Gonzalez, Claudio F" sort="Gonzalez, Claudio F" uniqKey="Gonzalez C" first="Claudio F." last="Gonzalez">Claudio F. Gonzalez</name><name sortKey="Lorca, Graciela L" sort="Lorca, Graciela L" uniqKey="Lorca G" first="Graciela L." last="Lorca">Graciela L. Lorca</name><name sortKey="Pagliai, Fernando A" sort="Pagliai, Fernando A" uniqKey="Pagliai F" first="Fernando A." last="Pagliai">Fernando A. Pagliai</name><name sortKey="Pan, Lei" sort="Pan, Lei" uniqKey="Pan L" first="Lei" last="Pan">Lei Pan</name><name sortKey="Torino, Maria I" sort="Torino, Maria I" uniqKey="Torino M" first="Maria I." last="Torino">Maria I. Torino</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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