AUTHOR=Gardner Christopher L. , Pagliai Fernando A. , Pan Lei , Bojilova Lora , Torino Maria I. , Lorca Graciela L. , Gonzalez Claudio F. 

TITLE=Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein in Liberibacter asiaticus

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01630

DOI=10.3389/fmicb.2016.01630

ISSN=1664-302X

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>