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Antimicrobials

Targeting virulence

Nature Reviews Microbiology volume 13, page 2 (2015)Cite this article

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With resistance to antibiotics on the rise, alternative therapeutic strategies to treat infectious diseases, such as anti virulence approaches, are urgently needed. Curtis et al. developed a broad-spectrum inhibitor (LED209) of the membrane-bound histidine kinase QseC, which is conserved in several Gram-negative pathogens and promotes the expression of key virulence genes. The authors showed that LED209 is highly selective and reduces the virulence of several multidrug-resistant pathogens in vitro and in infected mice. The compound has a unique mode of action by acting as a prodrug scaffold to deliver a 'warhead' that allosterically inhibits QseC signalling to decrease virulence gene expression. The authors also found that pre-treatment of mice with LED209 conferred low-level protection against bacterial infection.

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References

  1. Curtis, M. M. et al. QseC inhibitors as an antivirulence approach for Gram-negative pathogens. mBio 5, e02165-14 (2014)

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  1. Andrea Du Toit
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Du Toit, A. Targeting virulence. Nat Rev Microbiol 13, 2 (2015). https://doi.org/10.1038/nrmicro3407

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