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.
CITATION STYLE
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
Mendeley helps you to discover research relevant for your work.