Drug Repurposing: Tolfenamic Acid Inactivates PrbP, a Transcriptional Accessory Protein inLiberibacter asiaticus.
CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein inLiberibacter asiaticus. 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 PrbPin vitro. Chemical hits were analyzed for therapeutic efficacy againstL. asiaticusvia an infected leaf assay, where the transcriptional activity ofL. asiaticuswas found to decrease significantly after exposure to tolfenamic acid. Similarly, tolfenamic acid was found to inhibitL. asiaticusinfection in highly symptomatic citrus seedlings. Our results indicate that PrbP is an important transcriptional regulator for survival ofL. asiaticus in planta, and the chemicals identified by molecular screening assays could be used as a therapeutic treatment for huanglongbing disease.
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Christopher L
CL
Gardner
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Fernando A
FA
Pagliai
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Lei
L
Pan
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Lora
L
Bojilova
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Maria I
MI
Torino
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Graciela L
GL
Lorca
Microbiology and Cell Science Department, Genetics Institute & Institute of Food and Agricultural Science, University of Florida Gainesville, FL, USA.
Claudio F
CF
Gonzalez
Liberibacter asiaticus; antimicrobial; citrus; tolfenamic acid; transcriptional accessory protein