General Information:

Id: 3,827
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Damron FH and Goldberg JB(2012) Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa Mol. Microbiol. 84: 595-607 [PMID: 22497280]

Interaction Information:

Comment Expression of the alginate machinery and biosynthetic enzymes are controlled by the extracytoplasmic sigma factor, sigma-22 (AlgU/T). The key negative regulator of both sigma-22 activity and the mucoid phenotype is the cognate anti-sigma factor MucA. MucA sequesters sigma-22 to the inner membrane inhibiting the sigma factor's transcriptional activity.
Formal Description
Interaction-ID: 38285

gene/protein

mucA

decreases_activity of

gene/protein

algU

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38289

gene/protein

algU

increases_expression of

gene/protein

algD

Drugbank entries Show/Hide entries for algD
Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38290

gene/protein

algU

increases_expression of

gene/protein

alg8

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38292

gene/protein

algU

increases_expression of

gene/protein

alg44

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38293

gene/protein

algU

increases_expression of

gene/protein

algK

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38294

gene/protein

algU

increases_expression of

gene/protein

algE

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38296

gene/protein

algU

increases_expression of

gene/protein

algG

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38299

gene/protein

algU

increases_expression of

gene/protein

algX

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38300

gene/protein

algU

increases_expression of

gene/protein

algL

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38301

gene/protein

algU

increases_expression of

gene/protein

algI

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38304

gene/protein

algU

increases_expression of

gene/protein

algJ

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38305

gene/protein

algU

increases_expression of

gene/protein

algF

Comment P. aeruginosa sigma factor sigma-22 (AlgU/T) directs RNA polymerase to activate expression of the alginate biosynthetic genes, which are encoded in the algD alginate biosynthetic operon at loci PA3540 to PA3551.
Formal Description
Interaction-ID: 38307

gene/protein

algU

increases_expression of

gene/protein

algA

Comment Alginate genes are regulated by sigma-22, the loss of MucA-repression results in the constitutive mucoid phenotype. Sigma-22 (AlgU/T) and MucA are encoded in an operon (sigma-22-mucA-mucB-mucC-mucD) at loci PA0762-PA0766 on the PAO1 genome. MucB, just downstream of mucA, was identified as further negative regulator of sigma-22. MucB is a periplasmic protein that binds MucA.
Formal Description
Interaction-ID: 38318

gene/protein

mucB

decreases_activity of

gene/protein

algU

Comment Alginate genes are regulated by sigma-22, the loss of MucA-repression results in the constitutive mucoid phenotype. Sigma-22 (AlgU/T) and MucA are encoded in an operon (sigma-22-mucA-mucB-mucC-mucD) at loci PA0762-PA0766 on the PAO1 genome. MucB, just downstream of mucA, was identified as further negative regulator of sigma-22. MucB is a periplasmic protein that binds MucA.
Formal Description
Interaction-ID: 38321

gene/protein

mucB

interacts (colocalizes) with

gene/protein

mucA

Comment Alginate genes are regulated by sigma-22, the loss of MucA-repression results in the constitutive mucoid phenotype. Sigma-22 (AlgU/T) and MucA are encoded in an operon (sigma-22-mucA-mucB-mucC-mucD) at loci PA0762-PA0766 on the PAO1 genome. MucD is the final gene of the sigma-22 locus which encodes another negative regulator of alginate overproduction. MucD is a periplasmic chaperone protease.
Formal Description
Interaction-ID: 38323

gene/protein

mucD

decreases_activity of

gene/protein

algU

Comment Alginate forms a capsule that protects P. aeruginosa from various host defences, antibiotics and phagocytosis.
Formal Description
Interaction-ID: 38326

cellular component

(alginate)n

increases_activity of

process

antibiotic resistance

Comment Alginate forms a capsule that protects P. aeruginosa from various host defences, antibiotics and phagocytosis.
Formal Description
Interaction-ID: 38328

cellular component

(alginate)n

decreases_activity of

process

phagocytosis

Comment Membrane stress leads to expression of the sigma-22 regulon. D-cycloserine, an inhibitor of peptidoglycan synthesis induced a very high PalgD expression (sigma-22-dependent promoter fusion of algD with a chloramphenicol resistance gene (PalgD-cat), suggesting that inhibiting peptidoglycan synthesis caused membrane stress and affected the integrity of the cell. It has been shown that the sigma-22 gene was required for PalgD activity in the presence of d-cycloserine, suggesting that d-cycloserine induced loss of repression of sigma-22 by MucA. .
Formal Description
Interaction-ID: 38345

drug/chemical compound

Cycloserine

increases_activity of

gene/protein

algU

Drugbank entries Show/Hide entries for Cycloserine
Comment Membrane stress leads to expression of the sigma-22 regulon. D-cycloserine, an inhibitor of peptidoglycan synthesis induced a very high PalgD expression (sigma-22-dependent promoter fusion of algD with a chloramphenicol resistance gene (PalgD-cat), suggesting that inhibiting peptidoglycan synthesis caused membrane stress and affected the integrity of the cell. It has been shown that the sigma-22 gene was required for PalgD activity in the presence of d-cycloserine, suggesting that d-cycloserine induced loss of repression of sigma-22 by MucA. .
Formal Description
Interaction-ID: 38346

drug/chemical compound

Cycloserine

decreases_activity of

gene/protein

mucA

Drugbank entries Show/Hide entries for Cycloserine
Comment Experiments showed that without algW, sigma-22 (AlgU/T) was not activated and that AlgW was likely a protease of MucA and a positive regulator of sigma-22 activity. The overexpression of algW caused alginate overproduction.
Formal Description
Interaction-ID: 38349

gene/protein

algW

decreases_quantity of

gene/protein

mucA

Comment Experiments showed that without algW, sigma-22 (AlgU/T) was not activated and that AlgW was likely a protease of MucA and a positive regulator of sigma-22 activity. The overexpression of algW caused alginate overproduction.
Formal Description
Interaction-ID: 38381

gene/protein

algW

increases_quantity of

cellular component

(alginate)n

Comment P. aeruginosa MucE (PA4033), which has a C-terminus that is similar to proteins that activate DegS proteolysis of RseA in E. coli, has been shown to activate AlgW. When MucE is overexpressed AlgW cleaves MucA, which results in alginate overproduction.
Formal Description
Interaction-ID: 38383

gene/protein

mucE

increases_activity of

gene/protein

algW

Comment It has been shown in vitro that MucB binds the C-terminus of MucA, which protects MucA from proteolysis by AlgW.
Formal Description
Interaction-ID: 38388

gene/protein

mucB

decreases_activity of

gene/protein

algW

Comment AlgW and MucP are proteases that are positive regulators of alginate production due to their direct action upon MucA. The inner membrane protease MucP acts on MucA.
Formal Description
Interaction-ID: 38391

gene/protein

mucP

decreases_quantity of

gene/protein

mucA

Comment Chaperone-protease MucD regulates pathways leading to MucA proteolysis. Experiments suggests that MucD may not only degrade but may also chaperone misfolded proteins that leads to a slower rate of RIP (regulated intramembrane proteolysis) of MucA and therefore decreased alginate overproduction.
Formal Description
Interaction-ID: 38398

gene/protein

mucD

affects_quantity of

gene/protein

mucA

Comment The cytoplasmic protease complex ClpXP is responsible for removal of residual MucA leading to active sigma-22 (AlgU/T). ClpX contains two PDZ-like domains, which likely recognize unfolded or truncated MucA that is attached to sigma-22 and then facilitates degradation of MucA by ClpP.
Formal Description
Interaction-ID: 38402

gene/protein

clpP

interacts (colocalizes) with

gene/protein

clpX

Drugbank entries Show/Hide entries for clpP or clpX
Comment The cytoplasmic protease complex ClpXP is responsible for removal of residual MucA leading to active sigma-22 (AlgU/T). ClpX contains two PDZ-like domains, which likely recognize unfolded or truncated MucA that is attached to sigma-22 and then facilitates degradation of MucA by ClpP.
Formal Description
Interaction-ID: 38403

gene/protein

clpP

decreases_quantity of

gene/protein

mucA

Drugbank entries Show/Hide entries for clpP
Comment The cytoplasmic protease complex ClpXP is responsible for removal of residual MucA leading to active sigma-22 (AlgU/T). ClpX contains two PDZ-like domains, which likely recognize unfolded or truncated MucA that is attached to sigma-22 and then facilitates degradation of MucA by ClpP.
Formal Description
Interaction-ID: 38404

gene/protein

clpX

decreases_quantity of

gene/protein

mucA

Drugbank entries Show/Hide entries for clpX
Comment The periplasmic protease Prc (PA3257) acts on mutant MucA proteins, like MucA22 and may have a slight role in degradation of MucA.
Formal Description
Interaction-ID: 38406

gene/protein

prc

affects_quantity of

gene/protein

mucA

Comment High amounts of MV (membrane vesicle) were observed in the absence of MucD. Overexpression of mucD or algW caused decreased MV production.
Formal Description
Interaction-ID: 38408

gene/protein

mucD

decreases_quantity of

cellular component

bacterial membrane vesicle, MV

Comment High amounts of MV (membrane vesicle) were observed in the absence of MucD. Overexpression of mucD or algW caused decreased MV production.
Formal Description
Interaction-ID: 38416

gene/protein

algW

decreases_quantity of

cellular component

bacterial membrane vesicle, MV

Comment The periplasmic protease Prc (PA3257) acts on mutant MucA proteins, like MucA22 and may have a slight role in degradation of MucA.
Formal Description
Interaction-ID: 38418

gene/protein

prc

decreases_quantity of

gene/protein mutant

mucA-mut

Comment The mutation of mucA induces the transition to the mucoid phenotype and leads to loss of MucA function and therefore activation of sigma-22 (AlgU/T).
Formal Description
Interaction-ID: 38423

gene/protein mutant

mucA-mut

increases_activity of

gene/protein

algU

Comment The mutation of mucA induces the transition to the mucoid phenotype and leads to loss of MucA function and therefore activation of sigma-22 (AlgU/T).
Formal Description
Interaction-ID: 38424

gene/protein mutant

mucA-mut

increases_quantity of

cellular component

(alginate)n

Comment MucA22 is a common mutant MucA protein that arises in both CF (cystic fibrosis) isolates and laboratory strains.
Formal Description
Interaction-ID: 38425

process

P. aeruginosa infection, chronic

increases_activity of

gene/protein mutant

mucA-mut

Comment KinB has been characterized as a negative regulator of alginate overproduction in P. aeruginosa strain PAO1. In that study, it was observed that inactivation and deletion of kinB caused AlgW-dependent degradation of MucA.
Formal Description
Interaction-ID: 38476

gene/protein

kinB

decreases_quantity of

cellular component

(alginate)n

Comment KinB has been characterized as a negative regulator of alginate overproduction in P. aeruginosa strain PAO1. In that study, it was observed that inactivation and deletion of kinB caused AlgW-dependent degradation of MucA.
Formal Description
Interaction-ID: 38483

gene/protein

kinB

decreases_activity of

gene/protein

algW