scholarly journals The Pseudomonas aeruginosa Exoenzyme Y: A Promiscuous Nucleotidyl Cyclase Edema Factor and Virulence Determinant

2016 ◽  
pp. 67-85 ◽  
Author(s):  
K. Adam Morrow ◽  
Dara W. Frank ◽  
Ron Balczon ◽  
Troy Stevens
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Determinant ◽  
Edema Factor

scholarly journals Pseudomonas aeruginosa Expresses a Lethal Virulence Determinant, the PA-I Lectin/Adhesin, in the Intestinal Tract of a Stressed Host

2003 ◽  
Vol 238 (5) ◽  
pp. 754-764 ◽  
Author(s):  
Licheng Wu ◽  
Christopher Holbrook ◽  
Olga Zaborina ◽  
Emelia Ploplys ◽  
Flavio Rocha ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Intestinal Tract ◽  
Virulence Determinant

scholarly journals Reaction Products and the X-ray Structure of AmpDh2, a Virulence Determinant of Pseudomonas aeruginosa

2013 ◽  
Vol 135 (28) ◽  
pp. 10318-10321 ◽  
Author(s):  
Siseth Martínez-Caballero ◽  
Mijoon Lee ◽  
Cecilia Artola-Recolons ◽  
César Carrasco-López ◽  
Dusan Hesek ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Reaction Products ◽  
X Ray ◽  
Virulence Determinant

scholarly journals Exoenzyme Y Contributes to End-Organ Dysfunction Caused by Pseudomonas aeruginosa Pneumonia in Critically Ill Patients: An Exploratory Study

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 369
Author(s):  
Brant M. Wagener ◽  
Naseem Anjum ◽  
Sarah C. Christiaans ◽  
Morgan E. Banks ◽  
Jordan C. Parker ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Organ Dysfunction ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Lavage Fluid ◽  
Host Cells ◽  
Clinical Isolates ◽  
Icu Patients ◽  
Edema Factor ◽  
Host Infection

Pseudomonas aeruginosa is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, P. aeruginosa upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T and Y), ExoU has been shown in prior studies to associate with high mortality rates. Preclinical studies have shown that ExoY is an important edema factor in lung infection caused by P. aeruginosa, although its importance in clinical isolates of P. aeruginosa is unknown. We hypothesized that expression of ExoY would be highly prevalent in clinical isolates and would significantly contribute to patient morbidity secondary to P. aeruginosa pneumonia. A single-center, prospective observational study was conducted at the University of Alabama at Birmingham Hospital. Mechanically ventilated ICU patients with a bronchoalveolar lavage fluid culture positive for P. aeruginosa were included. Enrolled patients were followed from ICU admission to discharge and clinical P. aeruginosa isolates were genotyped for the presence of exoenzyme genes. Ninety-nine patients were enrolled in the study. ExoY was present in 93% of P. aeruginosa clinical isolates. Moreover, ExoY alone (ExoY+/ExoU−) was present in 75% of P. aeruginosa isolates, compared to 2% ExoU alone (ExoY−/ExoU+). We found that bacteria isolated from human samples expressed active ExoY and ExoU, and the presence of ExoY in clinical isolates was associated with end-organ dysfunction. This is the first study we are aware of that demonstrates that ExoY is important in clinical outcomes secondary to nosocomial pneumonia.

scholarly journals Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens

2021 ◽  
Author(s):  
Alexander Belyy ◽  
Felipe Merino ◽  
Undine Mechold ◽  
Stefan Raunser
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Vibrio Vulnificus ◽  
Binding Pocket ◽  
The Other ◽  
Host Cells ◽  
Actin Binding ◽  
Human Pathogens ◽  
Stabilization Mechanism ◽  
Allosteric Activation ◽  
Edema Factor

Several bacterial human pathogens secrete nucleotidyl cyclase toxins, that are activated by interaction with actin of the eukaryotic host cells. However, the underlying molecular mechanism of this process which protects bacteria from self-intoxication is unclear. Here, we report structures of ExoY from Pseudomonas aeruginosa and Vibrio vulnificus in complex with their corresponding activators F-actin and profilin-G-actin. The structures reveal that in contrast to the apo state, two flexible regions become ordered and interact strongly with actin. The specific stabilization of these regions results in an allosteric stabilization of the distant nucleotide binding pocket and thereby to an activation of the enzyme. Differences in the sequence and conformation of the actin-binding regions are responsible for the selective binding to either F- or G-actin. This specificity can be biotechnologically modulated by exchanging these regions from one toxin to the other. Other bacterial nucleotidyl cyclases, such as the anthrax edema factor and CyaA from Bortedella pertussis, that bind to calmodulin undergo a similar disordered-to-ordered transition during activation, suggesting that the allosteric activation-by-stabilization mechanism of ExoY is paradigmatic for all bacterial nucleotidyl cyclase toxins.

scholarly journals The Pseudomonas aeruginosa exoenzyme Y impairs endothelial cell proliferation and vascular repair following lung injury

2014 ◽  
Vol 306 (10) ◽  
pp. L915-L924 ◽  
Author(s):  
Trevor C. Stevens ◽  
Cristhiaan D. Ochoa ◽  
K. Adam Morrow ◽  
Matthew J. Robson ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Severe Pneumonia ◽  
Host Cells ◽  
Endothelial Cell Proliferation ◽  
Gap Formation ◽  
Pulmonary Endothelium ◽  
Edema Factor ◽  
Tissue Edema

Exoenzyme Y (ExoY) is a Pseudomonas aeruginosa toxin that is introduced into host cells through the type 3 secretion system (T3SS). Once inside the host cell cytoplasm, ExoY generates cyclic nucleotides that cause tau phosphorylation and microtubule breakdown. Microtubule breakdown causes interendothelial cell gap formation and tissue edema. Although ExoY transiently induces interendothelial cell gap formation, it remains unclear whether ExoY prevents repair of the endothelial cell barrier. Here, we test the hypothesis that ExoY intoxication impairs recovery of the endothelial cell barrier following gap formation, decreasing migration, proliferation, and lung repair. Pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains for 6 h, including one possessing an active ExoY (PA103 exoUexoT::Tc pUCPexoY; ExoY+), one with an inactive ExoY (PA103ΔexoUexoT::Tc pUCPexoYK81M; ExoYK81M), and one that lacks PcrV required for a functional T3SS (ΔPcrV). ExoY+ induced interendothelial cell gaps, whereas ExoYK81M and ΔPcrV did not promote gap formation. Following gap formation, bacteria were removed and endothelial cell repair was examined. PMVECs were unable to repair gaps even 3–5 days after infection. Serum-stimulated growth was greatly diminished following ExoY intoxication. Intratracheal inoculation of ExoY+ and ExoYK81M caused severe pneumonia and acute lung injury. However, whereas the pulmonary endothelial cell barrier was functionally improved 1 wk following ExoYK81M infection, pulmonary endothelium was unable to restrict the hyperpermeability response to elevated hydrostatic pressure following ExoY+ infection. In conclusion, ExoY is an edema factor that chronically impairs endothelial cell barrier integrity following lung injury.

Sign in / Sign up

Export Citation Format

Share Document