Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents.docVIP

Molecules 2010, 15, 780-792; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents Liang Yang *, Yang Liu, Claus Sternberg and S?ren Molin Department of Systems Biology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark; E-Mails: yali@bio.dtu.dk (Y.L.); cst@bio.dtu.dk (C.S.); sm@bio.dtu.dk (S.M.) * Author to whom correspondence should be addressed: E-Mail: ly@bio.dtu.dk; Tel.: +45-452-52-526; Fax: +45-45-887-328. Received: 7 December 2009; in revised form: 21 January 2010 / Accepted: 27 January 2010 / Published: 3 February 2010 Abstract: Pseudomonas aeruginosa is an opportunistic pathogen which is responsible for a wide range of infections. Production of virulence factors and biofilm formation by P. aeruginosa are partly regulated by cell-to-cell communication quorum-sensing systems. Identification of quorum-quenching reagents which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea epigallocatechin gallate (EGCG), which both function as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (ENR) from the bacterial type II fatty acid synthesis pathway. Our studies suggest that EGCG has a higher binding affinity towards ENR of P. aeruginosa and is an efficient quorum-quenching reagent. EGCG treatment was further shown to be able to attenuate the production of virulence factors and biofilm formation of P. aeruginosa. Keywords: Pseudomonas aeruginosa; quorum-quenching; enoyl-acyl carrier protein reductase; molecular dynamics simulation 1. Introduction Pseudomonas aeruginosa is an opportun