Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing

Neri Amara, Rachel Gregor, Josep Rayo, Rambabu Dandela, Erik Daniel, Nina Liubin, Hubertine Willems, Anat Ben-Zvi, Bastiaan P. Krom, Michael M. Meijler

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Emerging antibiotic resistance among human pathogens has galvanized efforts to find alternative routes to combat bacterial virulence. One new approach entails interfering with the ability of bacteria to coordinate population-wide gene expression, or quorum sensing (QS), thus inhibiting the production of virulence factors and biofilm formation. We have recently developed such a strategy by targeting LasR, the master regulator of QS in the opportunistic human pathogen Pseudomonas aeruginosa, through the rational design of covalent inhibitors closely based on the core structure of the native ligand. We now report several groups of new inhibitors, one of which, fluoro-substituted ITC-12, displayed complete covalent modification of LasR, as well as effective QS inhibition in vitro and promising in vivo results. In addition to their potential clinical relevance, this series of synthetic QS modulators can be used as a tool to further unravel the complicated QS regulation in P. aeruginosa.

Original languageEnglish (US)
Pages (from-to)825-835
Number of pages11
JournalChemBioChem
Volume17
Issue number9
DOIs
StatePublished - May 3 2016

Fingerprint

Quorum Sensing
Pathogens
Tuning
Biofilms
Virulence Factors
Gene expression
Modulators
Bacteria
Pseudomonas aeruginosa
Anti-Bacterial Agents
Ligands
Microbial Drug Resistance
Virulence
Gene Expression
Population

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Amara, N., Gregor, R., Rayo, J., Dandela, R., Daniel, E., Liubin, N., ... Meijler, M. M. (2016). Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. ChemBioChem, 17(9), 825-835. https://doi.org/10.1002/cbic.201500676

Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. / Amara, Neri; Gregor, Rachel; Rayo, Josep; Dandela, Rambabu; Daniel, Erik; Liubin, Nina; Willems, Hubertine; Ben-Zvi, Anat; Krom, Bastiaan P.; Meijler, Michael M.

In: ChemBioChem, Vol. 17, No. 9, 03.05.2016, p. 825-835.

Research output: Contribution to journalArticle

Amara, N, Gregor, R, Rayo, J, Dandela, R, Daniel, E, Liubin, N, Willems, H, Ben-Zvi, A, Krom, BP & Meijler, MM 2016, 'Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing', ChemBioChem, vol. 17, no. 9, pp. 825-835. https://doi.org/10.1002/cbic.201500676
Amara N, Gregor R, Rayo J, Dandela R, Daniel E, Liubin N et al. Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. ChemBioChem. 2016 May 3;17(9):825-835. https://doi.org/10.1002/cbic.201500676
Amara, Neri ; Gregor, Rachel ; Rayo, Josep ; Dandela, Rambabu ; Daniel, Erik ; Liubin, Nina ; Willems, Hubertine ; Ben-Zvi, Anat ; Krom, Bastiaan P. ; Meijler, Michael M. / Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. In: ChemBioChem. 2016 ; Vol. 17, No. 9. pp. 825-835.
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