General Information:

Id: 2,123
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Sadikot RT et al.(2005) Pathogen-host interactions in Pseudomonas aeruginosa pneumonia Am. J. Respir. Crit. Care Med. 171: 1209-1223 [PMID: 15695491]

Interaction Information:

Comment P. aeruginosa is the most prevalent chronic infection contributing to the pathogenesis of cystic fibrosis.
Formal Description
Interaction-ID: 17407

process

P. aeruginosa infection, chronic

increases_activity of

disease

Cystic fibrosis

Comment As a cause of ventilator-associated pneumonia (VAP), P. aeruginosa has a high mortality compared with other pathogens. P. aeruginosa is the second most common cause of nosocomial pneumonia after Staphylococcus aureus.
Formal Description
Interaction-ID: 17426

process

P. aeruginosa infection

increases_activity of

disease

Pneumonia

Comment Patients with CF (cystic fribrosis) have a high frequency of P. aeruginosa isolates with a phenotypic variant capable of forming biofilms related to a regulatory protein (PvrR).
Formal Description
Interaction-ID: 17446

gene/protein

pvrR

affects_activity of

in patients with CF
Comment Alginate production or mucoidy is another prominent feature of P. aeruginosa encountered in patients with CF (cystic fribrosis). Conversion to a mucoid strain, which is dependent on biofilm formation, has been associated with establishment of chronic infection in CF.
Formal Description
Interaction-ID: 17448

process

P. aeruginosa infection, chronic

increases_quantity of

phenotype

mucoid strain

in patients with CF
Comment Other phenotypic changes in P. aeruginosa isolated from patients with CF (cystic fribrosis) include lack of flagellin or pilin expression.
Formal Description
Interaction-ID: 17449

process

P. aeruginosa infection, chronic

decreases_quantity of

cellular component

flagellum

in patients with CF
Comment Other phenotypic changes in P. aeruginosa isolated from patients with CF (cystic fribrosis) include lack of flagellin or pilin expression.
Formal Description
Interaction-ID: 17450

process

P. aeruginosa infection, chronic

decreases_quantity of

cellular component

type IV pilus

in patients with CF
Comment Flagella are involved in the initial stages of pulmonary infection and activate interleukin (IL-)-8 production by binding to TLR5 on the apical surface of airway epithelial cells.
Formal Description
Interaction-ID: 17454

cellular component

flagellum

increases_quantity of

gene/protein

CXCL8

during pulmonary infection
Comment P. aeruginosa expresses a limited number of polar pili, which are involved in attachment to eukaryotic cells. They bind to the GalNac-beta1-4 gal moiety exposed on asialylated glycolipids and then activate NF-(kappa)B and proinflammatory gene expression through a receptor complex that includes asialoGM1, Toll-like receptor 2 (TLR2), and associated kinases in a lipid raft.
Formal Description
Interaction-ID: 17519

cellular component

type IV pilus

increases_activity of

Comment P. aeruginosa expresses a limited number of polar pili, which are involved in attachment to eukaryotic cells. They bind to the GalNac-beta1-4 gal moiety exposed on asialylated glycolipids and then activate NF-(kappa)B and proinflammatory gene expression through a receptor complex that includes asialoGM1, Toll-like receptor 2 (TLR2), and associated kinases in a lipid raft.
Formal Description
Interaction-ID: 17523

cellular component

type IV pilus

increases_activity of

gene/protein

TLR2

Drugbank entries Show/Hide entries for TLR2
Comment P. aeruginosa also produces polar flagella, which are critical for motility. Flagella are involved in the initial stages of pulmonary infection and activate interleukin (IL-)-8 production by binding to TLR5 on the apical surface of airway epithelial cells.
Formal Description
Interaction-ID: 17524

cellular component

flagellum

increases_activity of

gene/protein

TLR5

Comment P. aeruginosa encodes a type III secretion system that is a major determinant of virulence and allows the bacterium to inject toxins into the host cell.
Formal Description
Interaction-ID: 17527

process

P. aeruginosa infection

increases_activity of

process

T3SS

Comment The type III secretion system consists of three components: the secretion apparatus, the translocation or targeting apparatus, and the secreted toxins (effector proteins) and cognate chaperones. P. aeruginosa secretes four known effector proteins via type III secretion system: ExoS, ExoT, ExoU, and ExoY.
Formal Description
Interaction-ID: 17528

process

T3SS

increases_transport of

gene/protein

exoS

into the host cell
Comment The type III secretion system consists of three components: the secretion apparatus, the translocation or targeting apparatus, and the secreted toxins (effector proteins) and cognate chaperones. P. aeruginosa secretes four known effector proteins via type III secretion system: ExoS, ExoT, ExoU, and ExoY.
Formal Description
Interaction-ID: 17534

process

T3SS

increases_transport of

gene/protein

exoT

into the host cell
Comment The type III secretion system consists of three components: the secretion apparatus, the translocation or targeting apparatus, and the secreted toxins (effector proteins) and cognate chaperones. P. aeruginosa secretes four known effector proteins via type III secretion system: ExoS, ExoT, ExoU, and ExoY.
Formal Description
Interaction-ID: 17535

process

T3SS

increases_transport of

gene/protein

exoU

into the host cell
Comment The type III secretion system consists of three components: the secretion apparatus, the translocation or targeting apparatus, and the secreted toxins (effector proteins) and cognate chaperones. P. aeruginosa secretes four known effector proteins via type III secretion system: ExoS, ExoT, ExoU, and ExoY.
Formal Description
Interaction-ID: 17536

process

T3SS

increases_transport of

gene/protein

exoY

into the host cell
Comment ExoS was shown to induce TNF-alpha production via an MyD88-dependent pathway through activation of both TLR2 and TLR4.
Formal Description
Interaction-ID: 17537

gene/protein

exoS

increases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment ExoS was shown to induce TNF-alpha production via an MyD88-dependent pathway through activation of both TLR2 and TLR4.
Formal Description
Interaction-ID: 17539

gene/protein

exoS

increases_activity of

gene/protein

TLR2

Drugbank entries Show/Hide entries for TLR2
Comment ExoS was shown to induce TNF-alpha production via an MyD88-dependent pathway through activation of both TLR2 and TLR4.
Formal Description
Interaction-ID: 17540

gene/protein

exoS

increases_activity of

gene/protein

TLR4

Drugbank entries Show/Hide entries for TLR4
Comment ExoU is a member of the phospholipase A family of enzymes, possessing phospholipase A2 activity. In mammalian cells, the direct injection of ExoU has been shown to cause irreversible damage to cellular membranes and rapid necrotic death.
Formal Description
Interaction-ID: 17546

gene/protein

exoU

increases_activity of

process

cell death

Comment The neutralization of the type III secretion proteins has been shown to prevent septic shock and improve survival. In a mouse model of P. aeruginosa pneumonia, intravenous administration of polyclonal antibodies against PcrV (a protein involved in translocation of type III-secreted toxin) of P. aeruginosa resulted in complete survival of the animals.
Formal Description
Interaction-ID: 17549

gene/protein

pcrV

is_part_of

complex/PPI

T3SS needle-tip complex

Comment Complementary studies in a rabbit model of P. aeruginosa-induced septic shock associated with lung injury showed that treatment with anti-PcrV IgG significantly reduced lung injury, bacteremia, and plasma TNF-alpha levels compared with animals treated with control IgG.
Formal Description
Interaction-ID: 17551

gene/protein

pcrV

increases_quantity of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment P. aeruginosa has developed a mechanism to coordinate expression of genes important for adaptation to the environment. This response is controlled by quorum-sensing systems. Quorum-sensing signaling molecules are acyl homoserine lactones (AHL), which are freely diffusible. When a threshold AHL concentration is reached, AHL binds LasR/RhlR transcriptional activators to induce expression of certain genes. P. aeruginosa predominately makes two autoinducers: N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL, also called PAI-1) and N-butyryl-L-homoserine lactone (C4-HSL, also called PAI-2).
Formal Description
Interaction-ID: 17553

process

P. aeruginosa infection

affects_activity of

process

Acyl-HSL quorum sensing

Comment P. aeruginosa predominately makes two autoinducers: N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL, also called PAI-1) and N-butyryl-L-homoserine lactone (C4-HSL, also called PAI-2).
Formal Description
Interaction-ID: 17554

drug/chemical compound

N-(3-Oxododecanoyl)-HSL

affects_activity of

process

Acyl-HSL quorum sensing

induced by P. aeruginosa
Comment P. aeruginosa predominately makes two autoinducers: N-3-oxododecanoyl homoserine lactone (3-O-C12-HSL, also called PAI-1) and N-butyryl-L-homoserine lactone (C4-HSL, also called PAI-2).
Formal Description
Interaction-ID: 17555

drug/chemical compound

N-Butyryl-HSL

affects_activity of

process

Acyl-HSL quorum sensing

induced by P. aeruginosa
Comment The activation of the quorum-sensing cascade promotes the formation of biofilms, structured communities that coat mucosal surfaces and invasive devices. The formation of biofilms makes conditions more favorable for bacterial persistence in the lungs.
Formal Description
Interaction-ID: 17556

process

Acyl-HSL quorum sensing

increases_activity of

in P. aeruginosa infected host
Comment The activation of the quorum-sensing cascade promotes the formation of biofilms, structured communities that coat mucosal surfaces and invasive devices. The formation of biofilms makes conditions more favorable for bacterial persistence in the lungs.
Formal Description
Interaction-ID: 17557

process

P. aeruginosa infection

increases_activity of

Comment The production of alginate, the mucoexopolysaccharide characteristic of P. aeruginosa isolated from patients with CF (cyctic fibrosis), is a separate genetic event, apart from quorum sensing, even though these organisms also are enmeshed in a protective carbohydrate polymer.
Formal Description
Interaction-ID: 17558

process

Acyl-HSL quorum sensing

NOT affects_quantity of

cellular component

(alginate)n

in P. aeruginosa infected patients with CF
Comment Quorum-sensing molecules have the potential to directly modulate the host immune system. AHL (acyl homoserine lactones) induced cyclooxygenase-2 (COX-2) production in host cells through activation of NF-(kappa)B. COX-2 expression was linked to production of Prostaglandin E2 (PGE2), which has been shown to induce mucus secretion and promote vasodilation and edema.
Formal Description
Interaction-ID: 17562

process

Acyl-HSL quorum sensing

increases_activity of

in P. aeruginosa infected host
Comment Quorum-sensing molecules have the potential to directly modulate the host immune system. AHL (acyl homoserine lactones) induced cyclooxygenase-2 (COX-2) production in host cells through activation of NF-(kappa)B. COX-2 expression was linked to production of Prostaglandin E2 (PGE2), which has been shown to induce mucus secretion and promote vasodilation and edema.
Formal Description
Interaction-ID: 17563

increases_quantity of

gene/protein

PTGS2

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for PTGS2
Comment Quorum-sensing molecules have the potential to directly modulate the host immune system. AHL (acyl homoserine lactones) induced cyclooxygenase-2 (COX-2) production in host cells through activation of NF-(kappa)B. COX-2 expression was linked to production of Prostaglandin E2 (PGE2), which has been shown to induce mucus secretion and promote vasodilation and edema.
Formal Description
Interaction-ID: 17564

gene/protein

PTGS2

affects_quantity of

drug/chemical compound

Prostaglandin E2

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for PTGS2
Comment Quorum-sensing molecules have the potential to directly modulate the host immune system. AHL (acyl homoserine lactones) induced cyclooxygenase-2 (COX-2) production in host cells through activation of NF-(kappa)B. COX-2 expression was linked to production of Prostaglandin E2 (PGE2), which has been shown to induce mucus secretion and promote vasodilation and edema.
Formal Description
Interaction-ID: 17565

drug/chemical compound

Prostaglandin E2

increases_activity of

process

mucus secretion

in P. aeruginosa infected host
Comment Quorum-sensing molecules have the potential to directly modulate the host immune system. AHL (acyl homoserine lactones) induced cyclooxygenase-2 (COX-2) production in host cells through activation of NF-(kappa)B. COX-2 expression was linked to production of Prostaglandin E2 (PGE2), which has been shown to induce mucus secretion and promote vasodilation and edema.
Formal Description
Interaction-ID: 17566

drug/chemical compound

Prostaglandin E2

increases_activity of

process

vasodilation

in P. aeruginosa infected host
Comment It was shown that AHL (acyl homoserine lactones) were able to induce apoptosis of neutrophils and macrophages but not epithelial cells.
Formal Description
Interaction-ID: 17579

process

Acyl-HSL quorum sensing

increases_activity of

Comment P. aeruginosa produces two major siderophores: pyochelin and pyoverdin. These siderophores bind iron efficiently and are then taken up by the bacteria through specific cell-surface receptors. The siderophores are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself.
Formal Description
Interaction-ID: 17584

process

P. aeruginosa infection

increases_quantity of

drug/chemical compound

Pyochelin

Comment P. aeruginosa produces two major siderophores: pyochelin and pyoverdin. These siderophores bind iron efficiently and are then taken up by the bacteria through specific cell-surface receptors. The siderophores are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself.
Formal Description
Interaction-ID: 17585

process

P. aeruginosa infection

increases_quantity of

drug/chemical compound

Pyoverdine I

Comment The two major siderophores pyochelin and pyoverdin are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself. Pyoverdine up-regulated expression of genes required for synthesis of pyoverdine, exotoxin A, and PrpL protease (PMID: 11997446).
Formal Description
Interaction-ID: 17589

drug/chemical compound

Pyoverdine I

increases_expression of

gene/protein

toxA

Drugbank entries Show/Hide entries for toxA
Comment The two major siderophores pyochelin and pyoverdin are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself. Pyoverdine up-regulated expression of genes required for synthesis of pyoverdine, exotoxin A, and PrpL protease (PMID: 11997446).
Formal Description
Interaction-ID: 17590

drug/chemical compound

Pyoverdine I

increases_expression of

gene/protein

prpL

Comment The two major siderophores pyochelin and pyoverdin are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself. Pyoverdine up-regulated expression of genes required for synthesis of pyoverdine, exotoxin A, and PrpL protease (PMID: 11997446).
Formal Description
Interaction-ID: 17591

drug/chemical compound

Pyoverdine I

affects_quantity of

drug/chemical compound

Pyoverdine I

Comment Tissue invasion by P. aeruginosa is promoted by the production of elastase, alkaline proteases, hemolysins (phospholipase and lecithinase), cytotoxin (leukocidin), siderophores with their uptake systems, and diffusible pyocyanin pigment.
Formal Description
Interaction-ID: 17678

process

P. aeruginosa infection

increases_quantity of

drug/chemical compound

Pyocyanine

Comment The elastases disrupt the integrity of the epithelial barrier by disrupting epithelial cell tight junctions and interfering with mucociliary clearance.
Formal Description
Interaction-ID: 17682

gene/protein

lasB

decreases_activity of

Drugbank entries Show/Hide entries for lasB
Comment P. aeruginosa elastase degrades surfactant proteins A and D (SP-A and SP-D), which have an important role in innate immunity.
Formal Description
Interaction-ID: 17684

gene/protein

lasB

decreases_quantity of

gene/protein

SFTPA1

Drugbank entries Show/Hide entries for lasB or SFTPA1
Comment P. aeruginosa elastase degrades surfactant proteins A and D (SP-A and SP-D), which have an important role in innate immunity.
Formal Description
Interaction-ID: 17685

gene/protein

lasB

decreases_quantity of

gene/protein

SFTPD

Drugbank entries Show/Hide entries for lasB or SFTPD
Comment High concentrations of pyocyanin are detected in pulmonary secretions of patients with CF, where it exerts a proinflammatory effect, disrupts the bronchial epithelium, and impairs ciliary function.
Formal Description
Interaction-ID: 17686

drug/chemical compound

Pyocyanine

increases_activity of

in patients with CF
Comment Pyocyanin also interferes with the antioxidant defenses in the lung and facilitates oxidative damage to the lung epithelium through inhibition of catalase activity.
Formal Description
Interaction-ID: 17688

drug/chemical compound

Pyocyanine

affects_activity of

in the lung epithelium
Comment P. aeruginosa can cause direct tissue damage and necrosis, often a consequence of exotoxin A production.
Formal Description
Interaction-ID: 17697

gene/protein

toxA

increases_activity of

process

cell death

Drugbank entries Show/Hide entries for toxA
Comment Exotoxin A is an exceptionally potent ADP-ribosylating enzyme that enters eukaryotic cells by receptor-mediated endocytosis and catalyzes the ADP-ribosylation of eukaryotic elongation factor-2.
Formal Description
Interaction-ID: 17700

gene/protein

toxA

decreases_activity of

gene/protein

EEF2

Drugbank entries Show/Hide entries for toxA or EEF2
Comment Several bacterial components, including both P. aeruginosa flagella and pili, activate an intracellular calcium-dependent signaling cascade that includes Ras, Src, and Erk 1/2MAP (mitogen-activated protein) kinases.
Formal Description
Interaction-ID: 17709

cellular component

flagellum

increases_activity of

process

MAPK cascade

in P. aeruginosa infected host
Comment Several bacterial components, including both P. aeruginosa flagella and pili, activate an intracellular calcium-dependent signaling cascade that includes Ras, Src, and Erk 1/2MAP (mitogen-activated protein) kinases.
Formal Description
Interaction-ID: 17716

cellular component

type IV pilus

increases_activity of

process

MAPK cascade

in P. aeruginosa infected host
Comment Several bacterial components, including both P. aeruginosa flagella and pili, activate an intracellular calcium-dependent signaling cascade that includes Ras, Src, and Erk 1/2MAP (mitogen-activated protein) kinases.
Formal Description
Interaction-ID: 17717

cellular component

flagellum

increases_activity of

in P. aeruginosa infected host
Comment Several bacterial components, including both P. aeruginosa flagella and pili, activate an intracellular calcium-dependent signaling cascade that includes Ras, Src, and Erk 1/2MAP (mitogen-activated protein) kinases.
Formal Description
Interaction-ID: 17718

cellular component

type IV pilus

increases_activity of

in P. aeruginosa infected host
Comment Apoptosis induced by the CD95-CD95 ligand interaction requires clustering of the CD95 receptors, which involves the generation of ceramide by the action of acid sphingomyelinase on sphingolipids. P. aeruginosa infection can trigger activation of acid sphingomyelinase and induce the formation of lipid rafts containing CD95, which appear to regulate apoptosis and cytokine responses by infected cells.
Formal Description
Interaction-ID: 17724

process

P. aeruginosa infection

increases_activity of

gene/protein

SMPD1

Drugbank entries Show/Hide entries for SMPD1
Comment Apoptosis induced by the CD95-CD95 ligand interaction requires clustering of the CD95 receptors, which involves the generation of ceramide by the action of acid sphingomyelinase on sphingolipids. P. aeruginosa infection can trigger activation of acid sphingomyelinase and induce the formation of lipid rafts containing CD95, which appear to regulate apoptosis and cytokine responses by infected cells.
Formal Description
Interaction-ID: 17728

gene/protein

SMPD1

increases_quantity of

drug/chemical compound

N-Acylsphingosine

Drugbank entries Show/Hide entries for SMPD1
Comment The interaction of P. aeruginosa with macrophages occurs via multiple cell surface receptors and is accompanied by the formation of pseudopods.
Formal Description
Interaction-ID: 17732

process

P. aeruginosa infection

increases_activity of

Comment Alveolar macrophages, the resident mononuclear phagocytes of the lung, have roles in both the innate and adaptive immune responses to infection.
Formal Description
Interaction-ID: 17733

tissue/cell line

alveolar macrophage

increases_activity of

process

immune response

in P. aeruginosa infected host
Comment The recruitment of neutrophils is a major component of the protective host response to P. aeruginosa, and appears to outweigh the contributions of other immune cells, at least in the acute setting. The depletion of neutrophils results in excessive mortality after P. aeruginosa infection.
Formal Description
Interaction-ID: 17737

process

P. aeruginosa infection, acute

increases_activity of

Comment Neutralization of the receptor CXCR2 resulted in a striking increase in mortality, which was associated with a marked decrease in neutrophil recruitment and bacterial clearance.
Formal Description
Interaction-ID: 17754

gene/protein

CXCR2

increases_activity of

in P. aeruginosa infected host
Comment Studies in animal models confirmed that the presence of CD11a(b)/18 is required for neutrophil emigration to the lungs in response to P. aeruginosa infection.
Formal Description
Interaction-ID: 17755

gene/protein

ITGAL

increases_activity of

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for ITGAL
Comment Studies in animal models confirmed that the presence of CD11a(b)/18 is required for neutrophil emigration to the lungs in response to P. aeruginosa infection.
Formal Description
Interaction-ID: 17756

gene/protein

ITGAM

increases_activity of

in P. aeruginosa infected host
Comment Studies in animal models confirmed that the presence of CD11a(b)/18 is required for neutrophil emigration to the lungs in response to P. aeruginosa infection.
Formal Description
Interaction-ID: 17757

gene/protein

ITGB2

increases_activity of

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for ITGB2
Comment Mice deficient in uPAR were found to have diminished neutrophil recruitment in response to P. aeruginosa lung infection compared with the wild-type mice.
Formal Description
Interaction-ID: 17758

gene/protein

PLAUR

increases_activity of

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for PLAUR
Comment P. aeruginosa pyocyanin has been shown to induce apoptosis of neutrophils and may be a mechanism by which the bacteria resist host defenses, leading to persistent infection.
Formal Description
Interaction-ID: 17759

drug/chemical compound

Pyocyanine

increases_activity of

in P. aeruginosa infected host
Comment The type of T-cell response in the lung may contribute to the level of resistance to P. aeruginosa. A Th2-dominated pulmonary response is seen in susceptible strains, whereas mice that are resistant to P. aeruginosa infection show a Th1-dominated pulmonary response.
Formal Description
Interaction-ID: 17762

process

P. aeruginosa infection

increases_activity of

process

immune response

Comment P. aeruginosa flagella have been shown to initiate signaling through TLR5 and TLR2.
Formal Description
Interaction-ID: 17774

gene/protein

fliC

increases_activity of

gene/protein

TLR2

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for TLR2
Comment P. aeruginosa has been shown to signal through TLR4 with its LPS moiety. Although TLR4 is expressed in airway epithelial cells, it does not appear to be prominently involved in signaling of P. aeruginosa presented at the apical surface of polarized epithelial cells.
Formal Description
Interaction-ID: 17775

process

P. aeruginosa infection

increases_activity of

gene/protein

TLR4

Drugbank entries Show/Hide entries for TLR4
Comment MyD88 (the key adaptor protein used by TLRs)-dependent signaling is integral to the initiation of cytokine and inflammatory responses to pathogen.
Formal Description
Interaction-ID: 17781

gene/protein

TLR2

increases_activity of

gene/protein

MYD88

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for TLR2
Comment MyD88 (the key adaptor protein used by TLRs)-dependent signaling is integral to the initiation of cytokine and inflammatory responses to pathogen.
Formal Description
Interaction-ID: 17782

gene/protein

TLR4

increases_activity of

gene/protein

MYD88

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for TLR4
Comment MyD88 (the key adaptor protein used by TLRs)-dependent signaling is integral to the initiation of cytokine and inflammatory responses to pathogen.
Formal Description
Interaction-ID: 17783

gene/protein

TLR5

increases_activity of

gene/protein

MYD88

in P. aeruginosa infected host
Comment Both IL-1 and IL-18 activity impairs bacterial clearance in P. aeruginosa lung infections; however, the molecular mechanisms by which these cytokines impair host defense in this setting have not been elucidated.
Formal Description
Interaction-ID: 17784

gene/protein

IL18

increases_activity of

process

P. aeruginosa infection

Comment IL-10 is an antiinflammatory cytokine. Antiinflammatory cytokines are involved in regulating the potentially damaging effects of neutrophilic inflammation. IL-10 null mice show prolonged and excessive proinflammatory cytokine production and neutrophil infiltration in the airways after P. aeruginosa infection.
Formal Description
Interaction-ID: 17792

gene/protein

IL10

decreases_activity of

process

P. aeruginosa infection

Comment Administration of IL-4 enhances bacterial clearance from the lungs of wild-type mice and decreases mortality after infection. The protective effects of IL-4 may be related to its ability to modulate leukocyte function. IL-4 enhances expression of complement receptors CR1, CR3, and CR4 and increases complement-dependent phagocytosis.
Formal Description
Interaction-ID: 17794

gene/protein

IL4

decreases_activity of

process

P. aeruginosa infection

Comment LasA production by P. aeruginosa was found to markedly stimulate the shedding of syndecan-1 ectodomains, whereas other gram-negative bacteria had only low levels of activity to induce shedding. By enhancing the shedding of syndecan, P. aeruginosa takes advantage of a host-protective mechanism to promote its survival.
Formal Description
Interaction-ID: 17824

gene/protein

lasA

increases_activity of

of the proteoglycan SDC1, in P. aeruginosa infected host
Comment LasA production by P. aeruginosa was found to markedly stimulate the shedding of syndecan-1 ectodomains, whereas other gram-negative bacteria had only low levels of activity to induce shedding. By enhancing the shedding of syndecan, P. aeruginosa takes advantage of a host-protective mechanism to promote its survival.
Formal Description
Interaction-ID: 17827

gene/protein

lasA

decreases_quantity of

gene/protein

SDC1

in P. aeruginosa infected host
Comment Syndecan-1 null mice are resistant to P. aeruginosa lung infection, suggesting the importance of this mechanism in pathogenesis of P. aeruginosa pneumonia.
Formal Description
Interaction-ID: 17830

gene/protein

SDC1

increases_activity of

process

P. aeruginosa infection

Comment Surfactant proteins enhance the phagocytosis and killing of microbes. Both in vitro and in vivo studies provide evidence that SP-A and SP-D have important roles in the innate immune response to P. aeruginosa.
Formal Description
Interaction-ID: 17831

gene/protein

SFTPA1

affects_activity of

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for SFTPA1
Comment Surfactant proteins enhance the phagocytosis and killing of microbes. Both in vitro and in vivo studies provide evidence that SP-A and SP-D have important roles in the innate immune response to P. aeruginosa.
Formal Description
Interaction-ID: 17832

gene/protein

SFTPD

affects_activity of

in P. aeruginosa infected host
Drugbank entries Show/Hide entries for SFTPD
Comment Levels of SP-A and SP-D have been shown to be decreased in the lungs of patients with CF (cystic fribrosis).
Formal Description
Interaction-ID: 17833

process

P. aeruginosa infection, chronic

decreases_quantity of

gene/protein

SFTPA1

in patients with CF
Drugbank entries Show/Hide entries for SFTPA1
Comment Levels of SP-A and SP-D have been shown to be decreased in the lungs of patients with CF (cystic fribrosis).
Formal Description
Interaction-ID: 17834

process

P. aeruginosa infection, chronic

decreases_quantity of

gene/protein

SFTPD

in patients with CF
Drugbank entries Show/Hide entries for SFTPD
Comment In vitro studies support a role for SP-D in phagocytosis of mucoid and nonmucoid strains of P. aeruginosa. SP-D can enhance phagocytosis of P. aeruginosa expressing either smooth or rough LPS.
Formal Description
Interaction-ID: 17835

gene/protein

SFTPD

increases_activity of

process

phagocytosis

of mucoid and nonmucoid strains
Drugbank entries Show/Hide entries for SFTPD
Comment The recent success of azithromycin in CF may reflect its activity in blocking quorum-sensing systems in vivo.
Formal Description
Interaction-ID: 17839

drug/chemical compound

Azithromycin

decreases_activity of

process

Acyl-HSL quorum sensing

Drugbank entries Show/Hide entries for Azithromycin
Comment MyD88 (the key adaptor proteins used by TLRs)-dependent signaling is integral to the initiation of cytokine and inflammatory responses to both pathogens after infection of the lower respiratory tract; however, MyD88 is essential for innate immunity to P. aeruginosa but not S. aureus.
Formal Description
Interaction-ID: 17840

gene/protein

MYD88

affects_activity of

in P. aeruginosa infected host
Comment Alveolar macrophages participate in generating the host inflammatory response through activation of cell-surface receptors and production of mediators, such as cytokines and chemokines.
Formal Description
Interaction-ID: 17841

tissue/cell line

alveolar macrophage

affects_activity of

Comment Exotoxin A is an exceptionally potent ADP-ribosylating enzyme that enters eukaryotic cells by receptor-mediated endocytosis and catalyzes the ADP-ribosylation of eukaryotic elongation factor-2. This inhibits protein synthesis, ultimately leading to cellular death.
Formal Description
Interaction-ID: 23656

gene/protein

toxA

decreases_activity of

process

translation

Drugbank entries Show/Hide entries for toxA
Comment Exotoxin A is an exceptionally potent ADP-ribosylating enzyme that enters eukaryotic cells by receptor-mediated endocytosis and catalyzes the ADP-ribosylation of eukaryotic elongation factor-2. This inhibits protein synthesis, ultimately leading to cellular death.
Formal Description
Interaction-ID: 23678

gene/protein

EEF2

increases_activity of

process

translation

Drugbank entries Show/Hide entries for EEF2
Comment P. aeruginosa produces two major siderophores: pyochelin and pyoverdin. These siderophores bind iron efficiently and are then taken up by the bacteria through specific cell-surface receptors. The siderophores are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself.
Formal Description
Interaction-ID: 24223

drug/chemical compound

Pyochelin

increases_activity of

Comment P. aeruginosa produces two major siderophores: pyochelin and pyoverdin. These siderophores bind iron efficiently and are then taken up by the bacteria through specific cell-surface receptors. The siderophores are major virulence factors important not only for providing iron to support bacterial metabolic processes but also for controlling the expression of other P. aeruginosa virulence factors, such as exotoxin A, endoprotease, and pyoverdine itself.
Formal Description
Interaction-ID: 24227

drug/chemical compound

Pyoverdine I

increases_activity of

Comment CD1d-restricted T cells appear to play a key role in host defense against P. aeruginosa in acute infections. CD1 is a major histocompatibility complex (MHC) class I-like protein that is expressed on the macrophage and presents glycolipid antigens to CD1-restricted T cells. In a murine P. aeruginosa pneumonia model, CD1d knockout mice showed markedly reduced pulmonary eradication of P. aeruginosa compared with wild-type mice. The treatment of wild-type mice with alpha-galatosyl-ceramide, a lipid that activates CD1d-restricted T cells, was associated with rapid pulmonary clearance through enhanced phagocytosis by alveolar macrophages.
Formal Description
Interaction-ID: 24254

gene/protein

CD1D

decreases_activity of

process

P. aeruginosa infection, acute

Drugbank entries Show/Hide entries for CD1D
Comment MyD88 (the key adaptor proteins used by TLRs)-dependent signaling is integral to the initiation of cytokine and inflammatory responses to both pathogens after infection of the lower respiratory tract; however, MyD88 is essential for innate immunity to P. aeruginosa but not S. aureus.
Formal Description
Interaction-ID: 24257

gene/protein

MYD88

affects_activity of

to P. aeruginosa but not S. aureus
Comment The role of T cells is being investigated and suggests that a Th1-type response is beneficial to the host.
Formal Description
Interaction-ID: 24258

decreases_activity of

process

P. aeruginosa infection

Comment Alginate production or mucoidy is another prominent feature of P. aeruginosa encountered in patients with CF (cystic fribrosis). Conversion to a mucoid strain, which is dependent on biofilm formation, has been associated with establishment of chronic infection in CF.
Formal Description
Interaction-ID: 40196

cellular component

(alginate)n

increases_activity of

in patients with CF