Targeting QseC Signaling and Virulence for Antibiotic Development
Top Cited Papers
- 22 August 2008
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 321 (5892) , 1078-1080
- https://doi.org/10.1126/science.1160354
Abstract
Many bacterial pathogens rely on a conserved membrane histidine sensor kinase, QseC, to respond to host adrenergic signaling molecules and bacterial signals in order to promote the expression of virulence factors. Using a high-throughput screen, we identified a small molecule, LED209, that inhibits the binding of signals to QseC, preventing its autophosphorylation and consequently inhibiting QseC-mediated activation of virulence gene expression. LED209 is not toxic and does not inhibit pathogen growth; however, this compound markedly inhibits the virulence of several pathogens in vitro and in vivo in animals. Inhibition of signaling offers a strategy for the development of broad-spectrum antimicrobial drugs.Keywords
This publication has 18 references indexed in Scilit:
- Inter-kingdom signalling: communication between bacteria and their hostsNature Reviews Microbiology, 2008
- The biology and future prospects of antivirulence therapiesNature Reviews Microbiology, 2008
- In vivo negative selection screen identifies genes required for Francisella virulenceProceedings of the National Academy of Sciences, 2007
- Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 PathwayJournal of Biological Chemistry, 2007
- The QseC sensor kinase: A bacterial adrenergic receptorProceedings of the National Academy of Sciences, 2006
- Role of Salmonella enterica Serovar Typhimurium Two-Component System PreA/PreB in Modulating PmrA-Regulated Gene TranscriptionJournal of Bacteriology, 2006
- Small-Molecule Inhibitor of Vibrio cholerae Virulence and Intestinal ColonizationScience, 2005
- Humans as the World's Greatest Evolutionary ForceScience, 2001
- Role for a Phage Promoter in Shiga Toxin 2 Expression from a Pathogenic Escherichia coli StrainJournal of Bacteriology, 2001
- Quinolone Antibiotics Induce Shiga Toxin–Encoding Bacteriophages, Toxin Production, and Death in MiceThe Journal of Infectious Diseases, 2000