Chapter title |
The Pseudomonas aeruginosa Exoenzyme Y: A Promiscuous Nucleotidyl Cyclase Edema Factor and Virulence Determinant
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Chapter number | 5003 |
Book title |
Non-canonical Cyclic Nucleotides
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Published in |
Handbook of experimental pharmacology, January 2016
|
DOI | 10.1007/164_2016_5003 |
Pubmed ID | |
Book ISBNs |
978-3-31-952671-3, 978-3-31-952673-7
|
Authors |
K. Adam Morrow, Dara W. Frank, Ron Balczon, Troy Stevens |
Abstract |
Exoenzyme Y (ExoY) was identified as a component of the Pseudomonas aeruginosa type 3 secretion system secretome in 1998. It is a common contributor to the arsenal of type 3 secretion system effectors, as it is present in approximately 90% of Pseudomonas isolates. ExoY has adenylyl cyclase activity that is dependent upon its association with a host cell cofactor. However, recent evidence indicates that ExoY is not just an adenylyl cyclase; rather, it is a promiscuous cyclase capable of generating purine and pyrimidine cyclic nucleotide monophosphates. ExoY's enzymatic activity causes a characteristic rounding of mammalian cells, due to microtubule breakdown. In endothelium, this cell rounding disrupts cell-to-cell junctions, leading to loss of barrier integrity and an increase in tissue edema. Microtubule breakdown seems to depend upon tau phosphorylation, where the elevation of cyclic nucleotide monophosphates activates protein kinases A and G and causes phosphorylation of endothelial microtubule associated protein tau. Phosphorylation is a stimulus for tau release from microtubules, leading to microtubule instability. Phosphorylated tau accumulates inside endothelium as a high molecular weight, oligomeric form, and is then released from the cell. Extracellular high molecular weight tau causes a transmissible cytotoxicity that significantly hinders cellular repair following infection. Thus, ExoY may contribute to bacterial virulence in at least two ways; first, by microtubule breakdown leading to loss of endothelial cell barrier integrity, and second, by promoting release of a high molecular weight tau cytotoxin that impairs cellular recovery following infection. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 5 | 21% |
Student > Ph. D. Student | 3 | 13% |
Student > Doctoral Student | 2 | 8% |
Student > Master | 1 | 4% |
Other | 1 | 4% |
Other | 3 | 13% |
Unknown | 9 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 3 | 13% |
Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Immunology and Microbiology | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Unspecified | 1 | 4% |
Other | 4 | 17% |
Unknown | 10 | 42% |