Targeting QseC Signaling and Virulence for Antibiotic Development Export

@article{citeulike:3149367, 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. 10.1126/science.1160354}, author = {Rasko, David A. and Moreira, Cristiano G. and Li, De R. and Reading, Nicola C. and Ritchie, Jennifer M. and Waldor, Matthew K. and Williams, Noelle and Taussig, Ron and Wei, Shuguang and Roth, Michael and Hughes, David T. and Huntley, Jason F. and Fina, Maggy W. and Falck, John R. and Sperandio, Vanessa}, citeulike-article-id = {3149367}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1160354}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/321/5892/1078}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18719281}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18719281}, day = {22}, doi = {10.1126/science.1160354}, journal = {Science}, keywords = {antibiotic, drug}, month = {August}, number = {5892}, pages = {1078--1080}, posted-at = {2008-08-22 16:40:46}, priority = {0}, title = {Targeting QseC Signaling and Virulence for Antibiotic Development}, url = {http://dx.doi.org/10.1126/science.1160354}, volume = {321}, year = {2008} }

TY - JOUR ID - citeulike:3149367 L3 - citeulike-article-id:3149367 N2 - 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. 10.1126/science.1160354 IS - 5892 JF - Science EP - 1080 TI - Targeting QseC Signaling and Virulence for Antibiotic Development VL - 321 SP - 1078 KW - antibiotic KW - drug AU - Rasko, David AU - Moreira, Cristiano AU - Li, De AU - Reading, Nicola AU - Ritchie, Jennifer AU - Waldor, Matthew AU - Williams, Noelle AU - Taussig, Ron AU - Wei, Shuguang AU - Roth, Michael AU - Hughes, David AU - Huntley, Jason AU - Fina, Maggy AU - Falck, John AU - Sperandio, Vanessa PY - 2008/08/22/ UR - http://dx.doi.org/10.1126/science.1160354 ER -