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Open AccessArticle

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

1
Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
3
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
4
Center for Lung Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
5
Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
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Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
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Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA
8
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Departments of Surgery and Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
10
Center for Lung Injury and Repair, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Toxins 2020, 12(6), 369; https://doi.org/10.3390/toxins12060369
Received: 21 May 2020 / Revised: 31 May 2020 / Accepted: 1 June 2020 / Published: 4 June 2020
(This article belongs to the Special Issue Toxins and Lung 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. View Full-Text
Keywords: Type III secretion system; pneumonia; ExoU; tau; amyloid Type III secretion system; pneumonia; ExoU; tau; amyloid
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Wagener, B.M.; Anjum, N.; Christiaans, S.C.; Banks, M.E.; Parker, J.C.; Threet, A.T.; Walker, R.R.; Isbell, K.D.; Moser, S.A.; Stevens, T.; Alexeyev, M.F.; Audia, J.P.; Richter, W.; Hardy, K.S.; Saleh, L.A.; Morgan, C.; Pittet, J.-F. Exoenzyme Y Contributes to End-Organ Dysfunction Caused by Pseudomonas aeruginosa Pneumonia in Critically Ill Patients: An Exploratory Study. Toxins 2020, 12, 369.

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