Targeting QseC signaling and virulence for antibiotic development.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 18719281.
- Also identified by DOI 10.1126/science.1160354 and PMC identifier 2605406.
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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.
Medical subject headings
- Anti-Bacterial Agents
- Enterohemorrhagic Escherichia coli
- Escherichia coli Proteins
- Francisella tularensis
- Gram-Negative Bacterial Infections
- Protein Kinases
- Salmonella typhimurium
- Sulfonamides