Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

Abstract

Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.

Quorum sensing et quorum quenching : Comment bloquer la communication des bactéries pour inhiber leur virulence ?

“…Compte tenu de son rôle prépondérant, à la fois dans la virulence et la résistance bactérienne, le QS est devenu une cible privilégiée pour le développement de nouvelles stratégies thérapeutiques pour répondre aux problèmes posés par l'utilisation massive d'antibiotiques. Des approches mettant en oeuvre des inhibiteurs chimiques, des anticorps ou des enzymes ont été développées pour contrer les effets du QS [16]. Contrairement aux agents bactéricides, l'inhibition du QS cible le système de communication des bactéries et n'affecte pas directement leur survie.…”

“…Une attention particulière a été portée à la lactonase hyperthermophile SsoPox (Sulfolobus solfataricus paraoxonase) isolée de l'archée Sulfolobus solfataricus provenant des sources chaudes du Vésuve, pour le QQ de P. aeruginosa, à la fois in vitro, sur des isolats cliniques, et in vivo, dans un modèle de pneumonie développé chez le rat [30,31]. L'administration intratrachéale de l'enzyme, capable de dégrader les AHL, a ainsi permis d'augmenter le taux de survie chez l'animal d'un facteur 4. prometteurs ont été réalisés par incorporation d'enzymes dans les revêtements constituants les cathéters, les membranes, les capsules et les nanofibres, ainsi que pour d'autres applications thérapeutiques, comme des traitements topiques ou oraux par aérosolisation [16,39].…”

Dismantling the bacterial virulence program

“…Drugs that have been examined include synthetic antibodies as well as agonists and antagonists of autoinducers (Rutherford and Bassler, 2012;Reuter et al, 2016;Maille et al, 2017). Moreover, quorum quenching (QQ) enzymes that are able to degrade signalling molecules, such as AHLdegrading lactonases and acylases, (Dong et al, 2001;Lin et al, 2003) reduce the production of harmful virulence factors thereby inducing antimicrobial vulnerability (Remy et al, 2018). Despite extensive testing in animal models and promising results, only a few QS inhibitors have reached human trials (Remy et al, 2018) with no approved drugs to date.…”

“…Moreover, quorum quenching (QQ) enzymes that are able to degrade signalling molecules, such as AHLdegrading lactonases and acylases, (Dong et al, 2001;Lin et al, 2003) reduce the production of harmful virulence factors thereby inducing antimicrobial vulnerability (Remy et al, 2018). Despite extensive testing in animal models and promising results, only a few QS inhibitors have reached human trials (Remy et al, 2018) with no approved drugs to date. Thus, it remains to be seen whether QQ enzymes or QS inhibitors are realistic candidate therapies for the prevention and treatment of infectious diseases.…”

Kidneys and microbiota

“…Микроорганизмы в биологических системах общаются и координируют своё поведение с помощью секреции сигнальных молекул: олигопептидов у Гр+ бактерий, N-ацетилгомосеринов у Гр-микроорганизмов, которые выступают в качестве «слов» в языке бактерий, т.н. «чувство кворума», QS [2,3].…”