Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 August 2008:
Vol. 321. no. 5892, pp. 1078 - 1080
DOI: 10.1126/science.1160354
Prev | Table of Contents | Next

Reports

Targeting QseC Signaling and Virulence for Antibiotic Development

David A. Rasko,1* Cristiano G. Moreira,1 De Run Li,2 Nicola C. Reading,1 Jennifer M. Ritchie,3 Matthew K. Waldor,3 Noelle Williams,2 Ron Taussig,4 Shuguang Wei,2 Michael Roth,2 David T. Hughes,1 Jason F. Huntley,1 Maggy W. Fina,4 John R. Falck,2,4 Vanessa Sperandio1,2{dagger}

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.

1 Department of Microbiology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.
2 Department of Biochemistry, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.
3 Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Pharmacology, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.

* Present address: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

{dagger} To whom correspondence should be addressed. E-mail: vanessa.sperandio{at}utsouthwestern.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular, Antigenic, and Functional Characteristics of Ferric Enterobactin Receptor CfrA in Campylobacter jejuni.
X. Zeng, F. Xu, and J. Lin (2009)
Infect. Immun. 77, 5437-5448
   Abstract »    Full Text »    PDF »
Characterization of the Effects of Salicylidene Acylhydrazide Compounds on Type III Secretion in Escherichia coli O157:H7.
J. J. Tree, D. Wang, C. McInally, A. Mahajan, A. Layton, I. Houghton, M. Elofsson, M. P. Stevens, D. L. Gally, and A. J. Roe (2009)
Infect. Immun. 77, 4209-4220
   Abstract »    Full Text »    PDF »
Molecular insights into farm animal and zoonotic Salmonella infections.
M. P. Stevens, T. J. Humphrey, and D. J. Maskell (2009)
Phil Trans R Soc B 364, 2709-2723
   Abstract »    Full Text »    PDF »
The two-component system QseEF and the membrane protein QseG link adrenergic and stress sensing to bacterial pathogenesis.
N. C. Reading, D. A. Rasko, A. G. Torres, and V. Sperandio (2009)
PNAS 106, 5889-5894
   Abstract »    Full Text »    PDF »
Does the Trojan Horse Have an Achilles' Heel?.
G. Dougan (2009)
N. Engl. J. Med. 360, 83-84
   Full Text »    PDF »
Taste, Smell, and Anorexia in the Aged: What Can We Do To Help the Patients? An Initial Primer.
R. I. Henkin (2008)
Gerontology 13, 40-64
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)