Pseudomonas aeruginosa infection liberates transmissible, cytotoxic prion amyloids. FASEB J 2017 Jul;31(7):2785-2796
Date
03/21/2017Pubmed ID
28314768Pubmed Central ID
PMC5471513DOI
10.1096/fj.201601042RRScopus ID
2-s2.0-85021662814 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
Patients who recover from pneumonia subsequently have elevated rates of death after hospital discharge as a result of secondary organ damage, the causes of which are unknown. We used the bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, as a model for investigating this phenomenon. We show that infection of pulmonary endothelial cells by P. aeruginosa induces production and release of a cytotoxic amyloid molecule with prion characteristics, including resistance to various nucleases and proteases. This cytotoxin was self-propagating, was neutralized by anti-amyloid Abs, and induced death of endothelial cells and neurons. Moreover, the cytotoxin induced edema in isolated lungs. Endothelial cells and isolated lungs were protected from cytotoxin-induced death by stimulation of signal transduction pathways that are linked to prion protein. Analysis of bronchoalveolar lavage fluid collected from human patients with P. aeruginosa pneumonia demonstrated cytotoxic activity, and lavage fluid contained amyloid molecules, including oligomeric τ and Aβ. Demonstration of long-lived cytotoxic agents after Pseudomonas infection may establish a molecular link to the high rates of death as a result of end-organ damage in the months after recovery from pneumonia, and modulation of signal transduction pathways that have been linked to prion protein may provide a mechanism for intervention.-Balczon, R., Morrow, K. A., Zhou, C., Edmonds, B., Alexeyev, M., Pittet, J.-F., Wagener, B. M., Moser, S. A., Leavesley, S., Zha, X., Frank, D. W., Stevens, T. Pseudomonas aeruginosa infection liberates transmissible, cytotoxic prion amyloids.
Author List
Balczon R, Morrow KA, Zhou C, Edmonds B, Alexeyev M, Pittet JF, Wagener BM, Moser SA, Leavesley S, Zha X, Frank DW, Stevens TAuthor
Dara W. Frank PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytotoxins
Edema
Endothelial Cells
Humans
Mice
Neurons
Pneumonia, Bacterial
Prion Proteins
Pseudomonas Infections
Pseudomonas aeruginosa
Rats