Targeting QseC signaling and virulence for antibiotic development. Academic Article uri icon

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.

published proceedings

  • Science

author list (cited authors)

  • Rasko, D. A., Moreira, C. G., Li, D. R., Reading, N. C., Ritchie, J. M., Waldor, M. K., ... Sperandio, V.

complete list of 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

  • August 2008