Table 1.

Important virulence effectors of Pseudomonas aeruginosa in mammalian infection.

Virulence Factor	Category	Activity	Function	Ref.
Alginate	Extracellular polysaccharide	Biofilm formation	Contributes to biofilm formation and reduces susceptibility to antibiotics.	[15,16]
Alkaline protease (ArpA)	Exoenzyme	Zinc-dependent metalloprotease	Degrades host immune complements C1q, C2, and C3 and cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α.	[17,18,19]
Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif)	Phenazine	Epoxide hydrolase	Promotes sustained inflammation by hydrolysing the paracrine signal 14,15-epoxyeicosatrienoic acid that stimulates neutrophils to produce the pro-resolving lipid mediator 15-epi lipoxin A4. Cif increases the ubiquitination and lysosomal degradation of some ATP-binding cassette transporters (ABC) including CFTR, P-glycoprotein, and TAP1.	[20,21,22,23]
ExoA	Exoenzyme	Catalytic ADP-ribosylation of elongation factor 2	Inhibits protein synthesis and induces apoptosis in the host cell.	[24]
ExoS	Exoenzyme	Bifunctional toxin with Rho GTPase-activating protein (RhoGAP) activity and ADP-ribosyltransferase (ADPRT) activity	It blocks the reactive oxygen species burst in neutrophils by ADP-ribosylation of Ras, thereby preventing the activation of phosphoinositide-3-kinase (PI3K), which is required to stimulate the phagocytic NADPH-oxidase.	[25,26]
ExoT	Exoenzyme	Bifunctional toxin with RhoGAP activity and ADPRT activity	It impairs the production of reactive oxygen species burst in neutrophils and promotes the apoptosis of host cells by transforming host protein Crk by ADP-ribosylation into a cytotoxin and by activation of the intrinsic mitochondrial apoptotic pathway.	[27,28]
ExoU	Exoenzyme	Phospholipase A2	It becomes activated by interaction with ubiquitin or ubiquitinylated proteins in the cytosol of the host cell before localising to the cell membrane to catalyse fatty acids from a broad range of phospholipids and lysophospholipids.	[29,30]
ExoY	Exoenzyme	Secreted adenyl cyclase	Increases concentration of intracellular cAMP in host cells through disruption of the actin cytoskeleton and increased endothelial permeability.	[28]
Flagella	Organelle	Motility and adherence to surfaces	Elicits strong NFκB-mediated inflammatory response via signalling through toll-like receptor (TLR) 5 and a caspase-1-mediated response through Nod-like receptor, Ipaf. Provides bacterium with swimming motility in liquid.	[31]
LasA	Exoenzyme	Metallopeptidase, also known as staphylolysin	LasA acts with restricted specificity, predominantly at glycine-glycine peptide bonds, but also increases the elastinolytic activity of LasB.	[32]
LasB	Exoenzyme	Zinc-metalloprotease	Causes elastin degradation.	[17,33]
PlcH	Exoenzyme	Haemolytic phospholipase C	Releases phosphate esters from sphingomyelin and phosphatidylcholine.	[34]
PlcN	Exoenzyme	Non-haemolytic phospholipase C	Releases phosphate esters from phosphatidylserine and phosphatidylcholine.	[35]
PldA and PldB	Exoenzyme	Phospholipase D	Facilitates intracellular invasion of host eukaryotic cells by activation of the PI3K/ Akt pathway.	[36,37]
PrpL	Exoenzyme	Class IV protease, lysine endoproteinase	Inactivates a range of host defences including fibrinogen, plasminogen, immunoglobulin G, and complement proteins C1q and C3.	[38,39]
Pyocyanin	Phenazine	Redox-active zwitterion	Inhibits host cell respiration, ciliary function, and epidermal growth; disrupts calcium homeostasis and induces apoptosis in neutrophils.	[40]
Rhamnolipids	Surfactant	Biosurfactants	Participates in the maintenance of uninhabited channels surrounding biofilm communities, which serve to provide nutrients and oxygen to the colonies of bacteria. Biofilms can form on implants and on dead or living tissue. They are inherently difficult to eradicate with antibiotics due to the inability of antibiotic molecules to penetrate the extracellular matrix.	[41]
TplE	Exoenzyme	Phospholipase A1	Disrupts the endoplasmic reticulum and thereby promotes autophagy by the activation of the unfolded protein response.	[42]