Targeting QseC signaling and virulence for antibiotic development

David A. Rasko, Cristiano G. Moreira, Run Li De, Nicola C. Reading, Jennifer M. Ritchie, Matthew K. Waldor, Noelle S Williams, Ronald Taussig, Shuguang Wei, Michael G Roth, David T. Hughes, Jason F. Huntley, Maggy W. Fina, J R Falck, Vanessa Sperandio

Research output: Contribution to journalArticle

330 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1078-1080
Number of pages3
JournalScience
Volume321
Issue number5892
DOIs
StatePublished - Aug 22 2008

ASJC Scopus subject areas

  • General

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    Rasko, D. A., Moreira, C. G., De, R. L., Reading, N. C., Ritchie, J. M., Waldor, M. K., Williams, N. S., Taussig, R., Wei, S., Roth, M. G., Hughes, D. T., Huntley, J. F., Fina, M. W., Falck, J. R., & Sperandio, V. (2008). Targeting QseC signaling and virulence for antibiotic development. Science, 321(5892), 1078-1080. https://doi.org/10.1126/science.1160354