General Information:

Id: 3,140
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Engel J and Eran Y(2011) Subversion of mucosal barrier polarity by pseudomonas aeruginosa. Front Microbiol 2: 114 [PMID: 21747810]

Interaction Information:

Comment The mucosal barrier epithelium is comprised of one or more layers of epithelial cells that have specialized and distinct apical and basolateral surfaces, separated by tight junctions (TJs), that form selective permeability barriers between biological compartments. For opportunistic pathogens, like P. aeruginosa, the mucosal barrier represents a formidable challenge to bacterial-mediated damage or entry.
Formal Description
Interaction-ID: 28915

process

P. aeruginosa infection

decreases_activity of

of mucosal surface
Comment Studies of the interaction of P. aeruginosa with polarized epithelium in culture and in vivo show that the degree of polarity significantly affects the final outcome of infection. P. aeruginosa preferentially adheres to, enters, and injures wounded epithelium.
Formal Description
Interaction-ID: 28917

process

P. aeruginosa infection

decreases_activity of

Comment At the apical surface N-glycan chains were necessary and sufficient for P. aeruginosa binding, invasion, and cytotoxicity to MDCK and Calu-3 cells grown at various states of polarization.
Formal Description
Interaction-ID: 28918

cellular component

N-glycan

increases_activity of

process

P. aeruginosa infection

at the apical surface
Comment At the basolateral surface, the sulfation of heparan sulfate (HS) chains of HSPGs (heparan sulfate proteoglycans) was found to be critical for P. aeruginosa binding, cytotoxicity, and invasion. In incompletely polarized epithelium, HSPG abundance was increased at the apical surface, explaining at least in part the increased susceptibility of injured epithelium to P. aeruginosa colonization and damage.
Formal Description
Interaction-ID: 28919

cellular component

heparan sulfate proteoglycans, HSPGs

increases_activity of

process

P. aeruginosa infection

at the basolateral surface
Comment P. aeruginosa binding activates a central host signaling molecule, phosphatidylinositol 3-kinase (PI3K), which is required for the synthesis of PIP3 and for activation of a downstream effector, the serine/threonine kinase Akt.
Formal Description
Interaction-ID: 28920

process

P. aeruginosa infection

affects_activity of

Comment P. aeruginosa transforms apical into basolateral membrane, creating a local microenvironment that facilitates its colonization and entry into to the mucosal barrier. In polarized monolayers, P. aeruginosa binds near cell-cell junctions, where it activates and recruits PI3K to the apical surface, leading to a remarkable remodeling of the apical membrane in which protrusions enriched for PIP3 and actin form at the apical surface at the site of bacterial binding.
Formal Description
Interaction-ID: 28922

process

P. aeruginosa infection

increases_activity of

protrusions are deficient in apical markers and contain basolateral markers
Comment Out of the four known P. aeruginosa T3SS effectors proteins, ExoS and ExoT are logical candidates for interfering with cellular polarity and disrupting cell junction integrity.
Formal Description
Interaction-ID: 28926

gene/protein

exoS

decreases_activity of

Comment Out of the four known P. aeruginosa T3SS effectors proteins, ExoS and ExoT are logical candidates for interfering with cellular polarity and disrupting cell junction integrity.
Formal Description
Interaction-ID: 28928

gene/protein

exoS

decreases_activity of

Comment Out of the four known P. aeruginosa T3SS effectors proteins, ExoS and ExoT are logical candidates for interfering with cellular polarity and disrupting cell junction integrity.
Formal Description
Interaction-ID: 28929

gene/protein

exoT

decreases_activity of

Comment Out of the four known P. aeruginosa T3SS effectors proteins, ExoS and ExoT are logical candidates for interfering with cellular polarity and disrupting cell junction integrity.
Formal Description
Interaction-ID: 28930

gene/protein

exoT

decreases_activity of

Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28956

gene/protein

exoS

decreases_activity of

gene/protein

CDC42

Drugbank entries Show/Hide entries for CDC42
Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28957

gene/protein

exoS

decreases_activity of

gene/protein

RAC1

Drugbank entries Show/Hide entries for RAC1
Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28958

gene/protein

exoS

decreases_activity of

gene/protein

RHOA

Drugbank entries Show/Hide entries for RHOA
Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28959

gene/protein

exoT

decreases_activity of

gene/protein

CDC42

Drugbank entries Show/Hide entries for CDC42
Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28960

gene/protein

exoT

decreases_activity of

gene/protein

RAC1

Drugbank entries Show/Hide entries for RAC1
Comment The GAP domains of both ExoT and ExoS inactivate the RhoA family GTPases, Cdc42, Rac1, and RhoA.
Formal Description
Interaction-ID: 28961

gene/protein

exoT

decreases_activity of

gene/protein

RHOA

Drugbank entries Show/Hide entries for RHOA
Comment The results confirm that the ADPRT domain of ExoS is sufficient to disrupt epithelial barrier integrity. PAK strains expressing ExoS disrupted ZO-1, occludin, and ezrin localization, decreased membrane-associated occludin, and blocked ezrin phosphorylation as would be predicted from ADP ribosylation of ezrin.
Formal Description
Interaction-ID: 28962

gene/protein

exoS

decreases_activity of

gene/protein

TJP1

Comment The results confirm that the ADPRT domain of ExoS is sufficient to disrupt epithelial barrier integrity. PAK strains expressing ExoS disrupted ZO-1, occludin, and ezrin localization, decreased membrane-associated occludin, and blocked ezrin phosphorylation as would be predicted from ADP ribosylation of ezrin.
Formal Description
Interaction-ID: 28963

gene/protein

exoS

decreases_activity of

gene/protein

OCLN

Comment The results confirm that the ADPRT domain of ExoS is sufficient to disrupt epithelial barrier integrity. PAK strains expressing ExoS disrupted ZO-1, occludin, and ezrin localization, decreased membrane-associated occludin, and blocked ezrin phosphorylation as would be predicted from ADP ribosylation of ezrin.
Formal Description
Interaction-ID: 28964

gene/protein

exoS

decreases_activity of

gene/protein

EZR

Comment P. aeruginosa binding activates a central host signaling molecule, phosphatidylinositol 3-kinase (PI3K), which is required for the synthesis of PIP3 and for activation of a downstream effector, the serine/threonine kinase Akt.
Formal Description
Interaction-ID: 30866