Inhibitors of Bacterial Quorum Sensing – IP 1103

As antimicrobial resistance isa growing global threat, it is imperative to develop alternative therapeutic approaches. Quorum sensing (QS) is a typeof bacterial cell-to-cell signaling pathway mediated through the production,release, and detection of the small signaling molecules called autoinducers(AIs). Such communication allows bacterial control of crucial functionincluding virulence factors and biofilm formation. If achieved, the inhibition of QS wouldreduce bacterial pathogenicity, thus providing disease prevention and treatment.The mostcommon QS signaling molecule used by Gram-negative bacteria are acylhomoserinelactones (AHLs). The development of non-native acylhomoserine lactone (AHL)ligands has emerged as a promising new strategy to inhibit QS in Gram-negativebacteria. FIU inventors have developed new optically pure γ-lactams and cyclic azahemiacetals,bearing alkylthiomethyl substituents with different carbon chain lengths thatare capable of inhibiting bacterial QS pathways.These compounds have shown inhibition of thepathogenicity of Gram-negative bacteria such as Pseudomonasaeruginosa, an important human opportunistic pathogenaffecting immunocompromised individuals, cancer patients, burn victims, cysticfibrosis patients, and patients with impaired lung function. Anne Laure Schmitt Olivier 305-348-5948

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