Princeton University

Michiko E Taga

Bonnie L Bassler

Martin F Semmelhack

Douglas Tyler McKenzie

Shawn R Campagna

Frederick M Hughson

Stephen T Miller

Karina B Xavier

This invention relates to crystals comprising apo-LsrB and holo-LsrB. The structure of holo-LsrB identifies a tetrahydroxytetrahydrofuran derived from 4,5-dihydroxy-2,3-pentanedione (DPD) as the active autoinducer-2 (AI-2) molecule in. The X-ray crystallographic data can be used in a drug discovery method. Additionally the invention provides AI-2 analogs based on this discovery as well as pharmaceutical compositions containing those analogs.

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The present invention relates to the discovery of the lsr operon, the genes therein, and the polypeptides encoded by these genes. The present invention also includes strains with altered expression levels of the polypeptides encoded by the genes and the lsr operon relative to wild type cells. In some embodiments, the strains express a transporter that transports an autoinducer into the cell at a level higher than that of wild type cells. The present invention also includes methods for identifying compounds that modulate the transport of the autoinducer into cells.

Inhibitors of autoinducer transporters

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Somerville, MA, United States of America

Michiko E Taga