Analogues ofPseudomonas aeruginosasignalling molecules to tackle infections

Abstract

The emergence of antibiotic resistance coupled with the lack of investment by pharmaceutical companies necessitates a new look at how we tackle bacterial infections. An intriguing tactic is the interruption of bacterial communication systems. This non-biocidal approach would circumvent the evolutionary pressure on bacteria to mutate and develop resistance. In many pathogenic microorganisms, communication systems, collectively termed quorum sensing (QS), have been observed to control a number of bacterial behaviours including expression of virulence factors and the development of biofilms. QS signalling molecules and their biomimetics, therefore, represent a rational target for the disruption of cooperative behaviour and thus the development of novel antimicrobial strategies. Herein we review recent developments towards the interference of Pseudomonas aeruginosa QS using signalling molecules and their mimetics.

Quinolones Modulate Ghrelin Receptor Signaling: Potential for a Novel Small Molecule Scaffold in the Treatment of Cachexia

“…Quinolone compounds are mainly known for their widespread antimicrobial properties [ 51 ] but they have also been shown to exert different beneficial effects including antiulcer, antihistamine, or antimutagenic properties [ 34 ]. Recently, quinolones have been studied as signaling molecules for the interruption of quorum sensing in Pseudomonas aeruginosa and other pathogens [ 35 ]. Quinolones are very versatile structures that can be easily modified to enhance their interaction with key active sites.…”

“…The success of the quinolone moiety across numerous areas of biological importance is underpinned by the ability to selectively modify its molecular framework and, therefore, grant favorable biological properties. For example, recently, quinolones have been studied as signaling molecules for the interruption of quorum sensing in Pseudomonas aeruginosa and other pathogens [ 35 , 36 , 37 , 38 , 39 ]. The interactions have shown that exquisite specificity-of-structure is often required for biological activity, which renders the easily-decorated quinolones as an excellent molecular base-point.…”

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

“…In particular, the Pseudomonas quinolone signal (PQS) pathway, in which both PQS and 2‐heptyl‐4(1 H )‐quinolone (HHQ) act as autoinducers, has to be mentioned here. In‐depth SAR studies have led to various synthetic PQS/HHQ agonists or antagonists . One key discovery was that an antagonist of the PQS and HHQ receptor PqsR, 6‐nitro‐HHQ, can undergo in vivo conversion to 6‐nitro‐PQS, which turns out to be a potent PqsR modulator.…”

Pathogenetic Impact of Bacterial–Fungal Interactions

“…New therapeutic strategies targeting quorum sensing molecules and bacterial virulence factors are being tested with the aim to deliver more efficient antimicrobial treatment and to prevent development of drug resistance [87,88,89,90,91]. Such approaches were tested specifically against infections with P. aeruginosa and were able to disrupt the cell communication and to reduce the virulence [92,93,94,95]. Other studies have attempted to use antibiotics and antifungals in combination with quorum sensing molecules to treat bacterial–fungal infections [96].…”