Table 4.

Summary of the quorum-sensing systems employed by the ESKAPE organisms and the associated virulence factors.

Organism name	Quorum-sensing system	Major genes involved	Gene product	Function	Associated virulence factors	Molecule involved in quorum sensing	References
Enterococcus sp.	Fsr system	fsrA	FsrA	Regulates the expression of other genes of the fsr locus fsrBCD, ef1097, and protease coding genes gelE-sprE	• Degradation of host tissues • Regulation of autolysin N-acetylglucosaminidase (AtlA), which mediates eDNA release • Biofilm formation • Dissemination by mediating the cleavage of Ace protein	Gelatinase Biosynthesis Activating Pheromone (GBAP)	(Ali et al., 2017)
		fsrB	FsrB	Processes FsrD to produce GBAP
		fsrC	FsrC	Transmembrane protein that senses the level of GBAP in the extracellular environment
		fsrD	FsrD	Generates the propeptide FsrD, which later matures to form GBAP
	LuxS system	luxS	LuxS	Cleaves S-ribosylhomocysteine into homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which is later cyclized to form AI-2	• Biofilm formation • TP generation, translation, cell wall/membrane biogenesis, and nucleotide transport and metabolism	Autoinducer-2 (AI-2)	(Ali et al., 2017)
	Cytolysin-mediated quorum sensing	cylR1	CylR1	Regulatory protein that binds to CylLS at the membrane	• Ability to lyse the host cells	CylLS and CylLL	(WO5_03151 - Cytolysin immunity protein CylI - Enterococcus faecalis EnGen0354 - WO5_03151 gene & protein; Ali et al., 2017)
		cylR2	CylR2	Represses the expression of cytolysin
		cylLL	CylLL	Long subunit that autoinduces the expression of cytolysin
		cylLS	CylLS	Short subunit that autoinduces the expression of cytolysin
		cylM	CylM	Aids the post-translational modification of CylLL and CylLS
		cylB	CylB	Aids the processing and transport of CylLL and CylLS
		cylA	CylA	Activates CylLL and CylLS by cleaving 6 amino-acids
		cylI	CylI	Acts as a cytolysin immunity protein
Staphylococcus aureus	Agr (accessory gene regulator) system	agrA	AgrA	Regulates the expression of RNAII and RNAIII by binding to the respective promoters, P2 and P3. Also upregulates the expression of psmα and psmβ operons (phenol-soluble modulins (PSMs))	• Expression of toxins, peptidases, hemolysin, and exoenzymes • Expression of adhesins • Protection from the immune system • Dissemination of the biofilm and colonization	Autoinducing peptide (AIP)	(Le and Otto, 2015)
		agrB	AgrB	A transmembrane endopeptidase that aids in the maturation and the export of AIP
		agrC	AgrC	A transmembrane receptor protein that transduces the extracellular signal via AgrA
		agrD	AgrD	Generates the precursor of autoinducing peptide (AIP)
	LuxS system	luxS	LuxS	Aids the production of AI-2 and in the regulation of cap genes	• Capsule synthesis • Biofilm formation • Antibiotic susceptibility	Autoinducer-2 (AI-2)	(Zhao et al., 2010; Le and Otto, 2015)
Klebsiella pneumoniae	LuxS system	luxS	LuxS	Aids the production of AI-2	• Biofilm formation	Autoinducer-2 (AI-2)	(De Araujo et al., 2010; Chen L. et al., 2020)
Acinetobacter baumannii	AbaI/AbaR system	abaI/abaR	AbaI/AbaR	The autoinducing sensor protein AbaI generates AHL molecules, which can be bound by the AbaR receptors	• Biofilm formation • Motility	N-Acyl homoserine lactone (AHL)	(Saipriya et al., 2020)
Pseudomonas aeruginosa	LasI–LasR system	lasI/R	LasI and Las R	Upon activation, LasR–OdDHL and RhlR–BHL complexes further activate their expression by specifically binding to the promoter regions of las/rhl genes	• Biofilm formation • Expression of degradative enzymes like elastase, LasA protease, and alkaline protease • Production of exotoxins and hydrogen cyanide	N-Acyl homoserine lactones (HSL)-3oxo-C12	(Lee and Zhang, 2015)
	RhlI–RhlR system	rhlI/II	RhlI and RhlII		• Biofilm formation • Expression of degradative enzymes like rhamnolipids, pyocyanin, and elastase • Production of hydrogen cyanide	N-Acyl homoserine lactones (HSL)—C4
	Pseudomonas Quinolone System	pqsA	PqsA	Anthranilate-coenzyme A ligase that aids the formation of anthraniloyl-coenzyme A by activating anthranilate, marking the first step in PQS biosynthesis	• Expression of pyocyanin and rhamnolipids	4-Quinolone
		pqsB	PqsB	3-Oxoacyl-(acyl carrier protein) synthases that aid the formation of 2-heptyl-4-quinolone (HHQ), which acts as a precursor of PQS
		pqsC	PqsC
		pqsD	PqsD
		pqsE	PqsE	Metallo-β-lactamase associated with PQS-mediated phenotypes
		pqsH	PqsH	Flavin-dependent monooxygenase that hydroxylates HHQ
	IQS system	ambBCDE	AmbBCDE	Non-ribosomal peptide synthase gene cluster involved in IQS synthesis that crosslinks external stress-related cues with various inter-cellular quorum-sensing networks	• Expression of degradative enzymes like elastase, pyocyanin, and rhamnolipids	2-(2-Hydroxyphenyl)-thiazole-4-carbaldehyde
Enterobacter sp.	LuxS system	luxS	LuxS	QseA (quorum-sensing regulator A), and the LEE-encoded regulator, Ler	• Adhesion • Flagellin formation and motility	Autoinducer-2 (AI-2)	(Vendeville et al., 2005)