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J Med Chem. 2016 Oct 13;59(19):8879-8888. Epub 2016 Sep 15.

Truncated Autoinducing Peptides as Antagonists of Staphylococcus lugdunensis Quorum Sensing.

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School of Science and Health, Western Sydney University , Locked Bag 1797, Penrith South Dc, NSW 2751, Australia.
Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, Iowa 52242, United States.


Competitive quorum sensing (QS) antagonism offers a novel strategy for attenuating current multidrug resistant staphylococcal infections. To this end, a series of 10 truncated analogues based on the parent autoinducing peptides (AIPs) of Staphylococcus lugdunensis (groups I and II) and Staphylococcus epidermidis (groups I-III) were sequentially assessed against a newly developed Staphylococcus lugdunensis group I QS reporter strain. The truncated analogues based upon Staphylococcus lugdunensis AIP-1 (1) and AIP-2 (2) displayed respective IC50 values of 0.2 ± 0.01 μM and 0.3 ± 0.01 μM, while the truncated analogue of the Staphylococcus epidermidis AIP-1 (3) elicited an IC50 value of 2.7 ± 0.1 μM. These findings demonstrate the potential of cognate and "crosstalk" competitive quorum sensing inhibition using truncated AIPs as a means of attenuating staphylococcal infections in species beyond Staphylococcus aureus.

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