Targeting QseC Signaling and Virulence for Antibiotic Development Article (Web of Science)

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.

authors

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

publication date

  • 2008

webpage

published in

number of pages

  • 2

start page

  • 1078

end page

  • 1080

volume

  • 321

issue

  • 5892