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

319 Citations (Scopus)

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

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Virulence
Anti-Bacterial Agents
Poisons
Virulence Factors
Adrenergic Agents
Gene Expression
Membranes
Growth
Pharmaceutical Preparations
LED209
In Vitro Techniques
Histidine Kinase

ASJC Scopus subject areas

  • General

Cite this

Rasko, D. A., Moreira, C. G., De, R. L., Reading, N. C., Ritchie, J. M., Waldor, M. K., ... Sperandio, V. (2008). Targeting QseC signaling and virulence for antibiotic development. Science, 321(5892), 1078-1080. https://doi.org/10.1126/science.1160354

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

In: Science, Vol. 321, No. 5892, 22.08.2008, p. 1078-1080.

Research output: Contribution to journalArticle

Rasko, DA, Moreira, CG, De, RL, Reading, NC, Ritchie, JM, Waldor, MK, Williams, NS, Taussig, R, Wei, S, Roth, MG, Hughes, DT, Huntley, JF, Fina, MW, Falck, JR & Sperandio, V 2008, 'Targeting QseC signaling and virulence for antibiotic development', Science, vol. 321, no. 5892, pp. 1078-1080. https://doi.org/10.1126/science.1160354
Rasko DA, Moreira CG, De RL, Reading NC, Ritchie JM, Waldor MK et al. Targeting QseC signaling and virulence for antibiotic development. Science. 2008 Aug 22;321(5892):1078-1080. https://doi.org/10.1126/science.1160354
Rasko, David A. ; Moreira, Cristiano G. ; De, Run Li ; Reading, Nicola C. ; Ritchie, Jennifer M. ; Waldor, Matthew K. ; Williams, Noelle S ; Taussig, Ronald ; Wei, Shuguang ; Roth, Michael G ; Hughes, David T. ; Huntley, Jason F. ; Fina, Maggy W. ; Falck, J R ; Sperandio, Vanessa. / Targeting QseC signaling and virulence for antibiotic development. In: Science. 2008 ; Vol. 321, No. 5892. pp. 1078-1080.
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