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Targeting QseC signaling and virulence for antibiotic development.

Rasko, DA, Moreira, CG, Li, DER, Reading, NC, Ritchie, JM, Waldor, MK, Williams, N, Taussig, R, Wei, S, Roth, M , Hughes, DT, Huntley, JF, Fina, MW, Falck, JR and Sperandio, V (2008) Targeting QseC signaling and virulence for antibiotic development. Science, 321 (5892). pp. 1078-1080.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences
Authors :
NameEmailORCID
Rasko, DAUNSPECIFIEDUNSPECIFIED
Moreira, CGUNSPECIFIEDUNSPECIFIED
Li, DERUNSPECIFIEDUNSPECIFIED
Reading, NCUNSPECIFIEDUNSPECIFIED
Ritchie, JMUNSPECIFIEDUNSPECIFIED
Waldor, MKUNSPECIFIEDUNSPECIFIED
Williams, NUNSPECIFIEDUNSPECIFIED
Taussig, RUNSPECIFIEDUNSPECIFIED
Wei, SUNSPECIFIEDUNSPECIFIED
Roth, MUNSPECIFIEDUNSPECIFIED
Hughes, DTUNSPECIFIEDUNSPECIFIED
Huntley, JFUNSPECIFIEDUNSPECIFIED
Fina, MWUNSPECIFIEDUNSPECIFIED
Falck, JRUNSPECIFIEDUNSPECIFIED
Sperandio, VUNSPECIFIEDUNSPECIFIED
Date : 22 August 2008
Identification Number : 10.1126/science.1160354
Uncontrolled Keywords : Animals, Anti-Bacterial Agents, Enterohemorrhagic Escherichia coli, Escherichia coli Infections, Escherichia coli Proteins, Francisella tularensis, Gene Expression Regulation, Bacterial, Gram-Negative Bacterial Infections, Mice, Norepinephrine, Phosphorylation, Protein Kinases, Rabbits, Salmonella Infections, Animal, Salmonella typhimurium, Signal Transduction, Small Molecule Libraries, Sulfonamides, Tularemia, Virulence Factors
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 14:41
Last Modified : 31 Oct 2017 14:30
URI: http://epubs.surrey.ac.uk/id/eprint/326420

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