Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in Liberibacter asiaticus
Identifieur interne : 002223 ( Ncbi/Curation ); précédent : 002222; suivant : 002224Drug 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><idno type="wicri:Area/Ncbi/Merge">002223</idno><idno type="wicri:Area/Ncbi/Curation">002223</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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