Pseudomonas aeruginosa exoenzymes U and Y induce a transmissible endothelial proteinopathy (original) (raw)

2015, American journal of physiology. Lung cellular and molecular physiology

Here, we tested the hypothesis that Pseudomonas aeruginosa type 3 secretion system effectors ExoY and ExoU induce release of a high molecular weight endothelial tau, causing transmissible cell injury characteristic of an infectious proteinopathy. Both the bacterial delivery of ExoY and ExoU, and the conditional expression of an activity-attenuated ExoU, induced time-dependent pulmonary microvascular endothelial cell (PMVEC) gap formation that was paralleled by loss of intracellular tau and concomitant appearance of high molecular weight extracellular tau. Transfer of the high molecular weight tau in filtered supernatant onto naïve endothelial cells resulted in the intracellular accumulation of tau clusters, which was accompanied by cell injury, inter-endothelial gap formation, decreased endothelial network stability in Matrigel, and increased lung permeability. Tau oligomer monoclonal antibodies captured monomeric tau from filtered supernatant, but did not retrieve higher molecular ...

Sign up for access to the world's latest research.

checkGet notified about relevant papers

checkSave papers to use in your research

checkJoin the discussion with peers

checkTrack your impact