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.

Subscribe

Sci. Signal., 26 August 2008
Vol. 1, Issue 34, p. ec303
[DOI: 10.1126/scisignal.134ec303]

EDITORS' CHOICE

Microbiology Jam the Signal

Caroline Ash

Science, AAAS, Cambridge CB2 1LQ, UK

Many bacterial pathogens sense that they are in a potential host because they can detect adrenergic molecules. These organisms share a sensor kinase that picks up the signal and relays it to virulence gene loci, thus kicking in the responses needed to ensure bacterial establishment. This pathway makes a good target for broad-spectrum antibiotic development because virulence inhibition should not present a strong selective pressure for resistance. Rasko et al. have had some success with this approach using a nontoxic small-molecule inhibitor of the sensor kinase QseC, which blocks signaling in a sensitive and specific manner. In animal models, the inhibitor was somewhat effective against gastrointestinal infections with enterohemorrhagic E. coli and Salmonella typhimurium. Encouragingly, the lead molecule was more effective against the systemic pathogen Francisella tularensis: A single oral dose protected 80% of infected mice from death.

D. A. Rasko, C. G. Moreira, D. R. Li, N. C. Reading, J. M. Ritchie, M. K. Waldor, N. Williams, R. Taussig, S. Wei, M. Roth, D. T. Hughes, J. F. Huntley, M. W. Fina, J. R. Falck, V. Sperandio, Targeting QseC signaling and virulence for antibiotic development. Science 321, 1078-1080 (2008). [Abstract] [Full Text]

Citation: C. Ash, Jam the Signal. Sci. Signal. 1, ec303 (2008).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882