Targeting QseC signaling and virulence for antibiotic development

被引：398

作者：

Rasko, David A. ^{[1
]}

Moreira, Cristiano G. ^{[1
]}

Li, De Run ^{[2
]}

Reading, Nicola C. ^{[1
]}

Ritchie, Jennifer M. ^{[3
]}

Waldor, Matthew K. ^{[3
]}

Williams, Noelle ^{[2
]}

Taussig, Ron ^{[4
]}

Wei, Shuguang ^{[2
]}

Roth, Michael ^{[2
]}

Hughes, David T. ^{[1
]}

Huntley, Jason F. ^{[1
]}

Fina, Maggy W. ^{[4
]}

Falck, John R. ^{[2
,4
]}

Sperandio, Vanessa ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[3] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

来源：

SCIENCE | 2008年 / 321卷 / 5892期

关键词：

D O I：

10.1126/science.1160354

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1078 / 1080

页数：3

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