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Chem Biol. 2003 Jun;10(6):563-71.

Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer.

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Department of Biological Sciences, State University of New York, Buffalo, Buffalo, NY 14260, USA.


The autoinducer (AI) that initiates the quorum sensing (QS) signaling cascade in Pseudomonas aeruginosa is an acyl-homoserine lactone (acyl-HSL). We initiated a study of the requirements for binding of the AI to its protein effector LasR by synthesizing a library of analogs with the HSL moiety replaced with different amines and alcohols. We tested each compound for both agonist and antagonist activity using a QS-controlled reporter gene assay and found several new agonists and antagonists. A representative antagonist was further tested for its ability to inhibit virulence factors. This data progresses our understanding of the LasR-AI interaction toward the rational design of therapeutic inhibitors of QS.

[Indexed for MEDLINE]

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