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Science. 2008 Aug 22;321(5892):1078-80. doi: 10.1126/science.1160354.

Targeting QseC signaling and virulence for antibiotic development.

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  • 1Department of Microbiology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.

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.

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PMID:
18719281
[PubMed - indexed for MEDLINE]
PMCID:
PMC2605406
Free PMC Article

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