Natural Quorum Sensing Inhibitors – Small Molecules, Big Messages

Abstract

Due to the increasing emergence of antibiotic resistant bacterial strains within the past few decades, bacterial infections in general – and hospital‐borne infections, in particular – have become increasingly difficult to fight. It is therefore crucial to find new strategies to fight pathogenic bacteria. Targeted inhibition of quorum sensing (QS) presents a promising alternative. QS is a cell density‐dependent signaling pathway used for intra‐ and interspecies coordination of gene expression. In many bacteria, pathogenic phenotypes, as well as the expression of virulence factors, are under the control of QS regulons. A closer look at natural quorum sensing inhibitors may be helpful to identify potent compounds that can be used as alternatives to antibiotics. Moreover, it will also provide insight into the interactions between species that compete for the same habitat and resources. This review aims to summarize our current knowledge concerning natural QS inhibitors, as a starting point for the design and synthesis of new therapeutics to treat or prevent bacterial infections.

Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

“…Several antagonist peptides have been identified among natural compounds or designed to quench Gram-positive bacteria and many QSIs, mainly targeting Gram-negative QS and AI-2 mediated QS, have also been reported (Tang and Zhang, 2014 ; Singh et al, 2016 ). Such compounds can be natural products, like polyphenols isolated from tea or honey, ajoene from garlic, eugenol from clove or many others produced by marine organisms and fungi (Tang and Zhang, 2014 ; Delago et al, 2016 ), or they can be synthetic, such as 5-fluorouracil (5-FU) or azithromycin (Ueda et al, 2009 ; Swatton et al, 2016 ). Many QQ enzymes and macromolecules (Amara et al, 2011 ; Fetzner, 2015 ) as well as natural or synthetic QSIs (Dembitsky et al, 2011 ; Galloway et al, 2011 ; Stevens et al, 2011 ; Kalia, 2013 ; Delago et al, 2016 ) have been reported to date and exhaustively reviewed.…”

“…Such compounds can be natural products, like polyphenols isolated from tea or honey, ajoene from garlic, eugenol from clove or many others produced by marine organisms and fungi (Tang and Zhang, 2014 ; Delago et al, 2016 ), or they can be synthetic, such as 5-fluorouracil (5-FU) or azithromycin (Ueda et al, 2009 ; Swatton et al, 2016 ). Many QQ enzymes and macromolecules (Amara et al, 2011 ; Fetzner, 2015 ) as well as natural or synthetic QSIs (Dembitsky et al, 2011 ; Galloway et al, 2011 ; Stevens et al, 2011 ; Kalia, 2013 ; Delago et al, 2016 ) have been reported to date and exhaustively reviewed. Patents associated with these compounds (Pan and Ren, 2009 ; Romero et al, 2012 ; Jiang and Li, 2013 ) as well as routes to access novel molecules (Scutera et al, 2014 ) have also been discussed.…”

Virtual Screening and Biomolecular Interactions of CviR-Based Quorum Sensing Inhibitors Against Chromobacterium violaceum

“…Taken together, interfering this mechanism would have an astounding impact over the bacterial resistance and its control (Uroz et al, 2009 ; Kalia, 2015 ). Numerous studies have been published related to quorum sensing inhibitors (QSIs) which rationalize the capability of this strategy (Ren et al, 2005 ; Rasmussen and Givskov, 2006 ; Ni et al, 2008 ; Kalia, 2013 ; Brackman and Coenye, 2015 ; Coughlan et al, 2016 ; Delago et al, 2016 ).…”

Quorum Sensing Inhibitors from the Sea Discovered Using Bacterial N-acyl-homoserine Lactone-Based Biosensors

“…They include halogenated furanones, ( 56 ) [44,109], betonicine ( 57 ), cis -betonicine ( 58 ), floridoside ( 59 ), and isethionic acid ( 60 ) (Figure 11). They display an inhibition activity on QS mechanisms mediated by C 8 -AHL lactone and the TraR transcriptional activator protein [38,50,51,110]. ICR-FT/MS analysis revealed the presence of 2-dodecanoyloxyethanesulfonate ( 61 ) (Figure 11), in Asparagopsis taxiformis , as the lead molecule responsible for QSI activity based on Serratia liquefacien s MG44 and C. violaceum CV026 bioassays.…”