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dc.contributor.authorFong, Julyen
dc.contributor.authorMortensen, Kim T.en
dc.contributor.authorNørskov, Amalieen
dc.contributor.authorQvortrup, Katrineen
dc.contributor.authorYang, Liangen
dc.contributor.authorTan, Choon Hongen
dc.contributor.authorGivskov, Michaelen
dc.contributor.authorNielsen, Thomas Eilanden
dc.identifier.citationFong, J., Mortensen, K. T., Nørskov, A., Qvortrup, K., Yang, L., Tan, C. H., . . . Givskov, M. (2019). Itaconimides as novel quorum sensing inhibitors of Pseudomonas aeruginosa. Frontiers in Cellular and Infection Microbiology, 8, 443-. doi:10.3389/fcimb.2018.00443en
dc.description.abstractPseudomonas aeruginosa is known as an opportunistic pathogen that often causes persistent infections associated with high level of antibiotic-resistance and biofilms formation. Chemical interference with bacterial cell-to-cell communication, termed quorum sensing (QS), has been recognized as an attractive approach to control infections and address the drug resistance problems currently observed worldwide. Instead of imposing direct selective pressure on bacterial growth, the right bioactive compounds can preferentially block QS-based communication and attenuate cascades of bacterial gene expression and production of virulence factors, thus leading to reduced pathogenicity. Herein, we report on the potential of itaconimides as quorum sensing inhibitors (QSI) of P. aeruginosa. An initial hit was discovered in a screening program of an in-house compound collection, and subsequent structure-activity relationship (SAR) studies provided analogs that could reduce expression of central QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin), and also successfully lead to the eradication of P. aeruginosa biofilms in combination with tobramycin. Further studies on the cytotoxicity of compounds using murine macrophages indicated no toxicity at common working concentrations, thereby pointing to the potential of these small molecules as promising entities for antimicrobial drug development.en
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en
dc.description.sponsorshipMOE (Min. of Education, S’pore)en
dc.format.extent11 p.en
dc.relation.ispartofseriesFrontiers in Cellular and Infection Microbiologyen
dc.rights© 2019 Fong, Mortensen, Nørskov, Qvortrup, Yang, Tan, Nielsen and Givskov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectQuorum Sensingen
dc.titleItaconimides as novel quorum sensing inhibitors of Pseudomonas aeruginosaen
dc.typeJournal Articleen
dc.contributor.schoolSchool of Physical and Mathematical Sciencesen
dc.contributor.researchSingapore Centre for Environmental Life Sciences and Engineeringen
dc.description.versionPublished versionen
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