Quorum Quenching: A Potential Target for Antipseudomonal Therapy

Figures & data

Figure 1 The LuxR/AHL-mediated quorum sensing the regulation of the target genes’ expressions in P. aeruginosa. At a threshold level of AHL, a positive feedback loop is formed causing more AHL to be synthesized. Afterward, the reaction takes place between the AHLs and the LuxR receptor in the cytoplasm of the cell, leading to target genes’ expression of quorum sensing.

Figure 2 Graphical plot of the quorum-sensing system of P. aeruginosa. The AIs 3OC12-HSL, C4-HSL, and PQS/HHQ are synthesized by the AIs synthases, LasI, RhlI, and PqsABCDE, respectively. AIs are also identified by the receptors in the cell cytoplasm LasR, RhlR, and PqsR. Protein receptors in the cell cytoplasm regulate the expression of its corresponding AIs synthase as well as new targets, as demonstrated by the arrows. Arrows labeled (+) demonstrate a positive feedback.

Figure 3 Schematic diagram demonstrating quorum sensing inhibitors compounds of P. aeruginosa.

Table 1 Herbal Extracts as Quorum Sensing Inhibitors and Their Effects on the P. aeruginosa QS System

Quorum Sensing Inhibitor Compounds	Quorum Sensing Efficacy	Ref.
Coumarin	Production of biofilm and pathogenic factors production	[^Citation76]
Pistacia atlantica crude extract	Production of biofilm and pyocyanin secretion	[^Citation11]
Curcumin	Motility phenotypes and production of biofilm	[^Citation131]
Ginseng	Production of LasA and LasB and synthesis of the AHL molecules	[^Citation141]
Baicalin	Production of biofilm and pathogenic factors (protease, elastase, pyocyanin, rhamnolipid, motilities and exotoxin A)	[^Citation142]
Flavonoids (naturally-produced plant Metabolites)	LasR and RhlR receptors	[^Citation143]
Ajoene, a Sulfur-Rich Molecule from Garlic	Pathogenic factors production	[^Citation144]
Berberine	Production of biofilm, secretion of protease, pyoverdin, pyocyanin and the expressions of lasI, lasR, rhlI, rhlR genes	[^Citation133]
Trans-cinnamaldehyde	Secretion of protease, elastase, pyocyanin and production of biofilm and the expressions of lasI, lasR, rhlI, rhlR genes	[^Citation145]
Salicylic acid	Secretion of protease, elastase, pyocyanin and production of biofilm and the expressions of lasI, lasR, rhlI, rhlR genes	[^Citation145]
Phillyrin	Pyocyanin, rhamnolipid, elastase, swimming and twitching motility and biofilm formation	[^Citation146]
Trans-anethole	Swarming motility, secretion of protease, elastase, pyocyanin and the expressions of lasB gene	[^Citation147]
Cinnamic acid	Secretion of pyocyanin, proteases, elastase and production biofilm	[^Citation148]
Hordenine	Swarming motility, secretion of pyocyanin, elastase, rhamnolipid, production of biofilm and the expressions of lasI, lasR, rhlI, rhlR genes	[^Citation149]
Eugenol from clove extract	Pathogenic factors and production of biofilm	[^Citation150]
Ocimum sanctum	Secretion of pyocyanin, protease, elastase and production of biofilm	[^Citation151]
Musa paradisiaca	Pyocyanin, protease, elastase and biofilm formation	[^Citation151]
Caffeine	Motility phenotypes	[^Citation151]
Methanolic extract of Phyllanthus amarus	Motility phenotypes, pyocyanin secretion	[^Citation152]
Zingerone	Motility phenotypes, production of biofilm and pathogenic factors production	[^Citation153]
Combretum albiflorum	Elastase secretion and production of biofilm	[^Citation154]
Allium sativum (garlic) extract	Production of biofilm, elastase secretion	[^Citation155,Citation156]
FL fraction of Psidium guajava L	Virulence factors production and production of biofilm	[^Citation157]
Clove oil	Protease, chitinase and pyocyanin secretion, swimming motility and production of biofilm	[^Citation158]
The methanol extract of fenugreek	Protease, LasB elastase, pyocyanin and chitinase production, swarming motility and production of biofilm	[^Citation159]
The dichloromethane extract of Cordiagilletii	Pyocyanin secretion, the expression of genes lasB, rhlA, lasI, lasR, rhlI, and rhlR genes and production of biofilm	[^Citation160]
Manilkara zapota	Pyocyanin, protease and elastase secretion and production of biofilm	[^Citation151]
Diarylheptanoids from the barks of Alnus viridis and Alnus glutinosa	Pyocyanin secretion, twitching motility and production of biofilm	[^Citation161]
Gingerol	Exoprotease, rhamnolipid and pyocyanin secretion and biofilm formation	[^Citation162]
Diterpene phytol	Pyocyanin secretion, twitching motility and production of biofilm	[^Citation163]

Table 2 Synthetic Quorum Sensing Inhibitors, Their Targets, and Effects on the P. aeruginosa QS system

Quorum Sensing Inhibitor Compounds	Target	Quorum Sensing Efficacy	Ref.
N-decanoyl-L-homoserine benzyl ester	AHL-mediated	Protease, elastase, rhamnolipid secretion and motility phenotypes	[^Citation164]
Synthetic triazole containing analogs of AHL	LuxR-LasR analogs	LasR receptor	[^Citation165]
N-(indole-3-butanoyl)-L-HSL	AHL-mediated	Pathogenic factors production, production of biofilm	[^Citation166]
2-heptyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-	PqsR analog	Virulence factor production	[^Citation115]
N-(heptyl-sulfanyl acetyl)-L-HSL (HepS-AHL)	AHL-mediated	transcriptional regulator - LasR	[^Citation167]
N-arylglyoxamide Derivatives	LasR analog	Pyocyanin secretion	[^Citation168]
Diarylheptanoids	AHL-mediated	Production of biofilm and pyocyanin secretion	[^Citation161]
Aspirin	AHL-mediated	Virulence factor production, expressions of lasI, lasR, rhlI, rhlR, pqsA and pqsR genes and expression of Pseudomonas toxins exoS and exoY	[^Citation128]
Meloxicam and Piroxicam	AHL-mediated	LasR and PqsE protein	[^Citation129]
N-decanoyl-L-homoserine benzyl ester	AHL-mediated	Virulence factors production	[^Citation164]
3-nitro phenylacetanoyl HL	AHL-mediated	LasR reporter	[^Citation169]
1,3-benzoxazol-2(3 H)-one, 5-chloro-1,3-benzoxazol-2(3 H)-one, 6-methyl-1,3-benzoxazol-2(3 H)-one, and 5-methyl-1,3-benzoxazol-2(3 H)-one	Unknown	Elastase secretion, production of biofilm and motility phenotypes	[^Citation170]
(S,E)-2-hydroxy-N-(3-hydroxy-5-(hydroxymethyl)-2-27 methylpyridin-4-yl)propane hydrazide (pyridoxal lactohydrazone)	Unknown	Motility phenotypes, production of biofilm and pyocyanin secretion	[^Citation171]
Diastereomeric 2-methoxycyclopentyl	AHL-mediated	Pigmentation production	[^Citation172]
benzamide-benzimidazole	Transcriptional regulator	Reduced acute and persistent pathogenicity	[^Citation12]
(S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene) propane hydrazide (lacto hydrazone)	Unknown	Motility phenotypes, production of biofilm and pyocyanin secretion	[^Citation173]
Meta-bromo-thiolactone	LasR/RhlR analogs	Secretion of pyocyanin and production of biofilm	[^Citation174]

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