Klebsiella pneumoniae Isolated from Critically Ill Patient with Nosocomial Pneumonia Elicits a Proteinopathy

Abstract

Abstract Introduction/Objective Gram-negative opportunist Klebsiella pneumoniae has been identified by the World Health Organization as a critical threat partially due to its prevalence in nosocomial pneumonia. Survivors often suffer increased long-term morbidity and mortality secondary to end-organ damage, including impaired cognition. Pseudomonas aeruginosa lung infection generates an endothelial-derived tauopathy, yet whether K. pneumoniae infection elicits this phenomenon is unknown. We hypothesize K. pneumoniae infection triggers pathogenic tau release from endothelial cells, contributing to an infection-induced proteinopathy. Methods/Case Report We utilized wildtype, control, and tau-/- pulmonary microvascular endothelial cells (PMVECs). Tau was monitored via immunoblotting. K. pneumoniae (Kp 1-008) was isolated from the bronchoalveolar lavage of a critically ill patient diagnosed with a monomicrobial nosocomial pneumonia. Supernatants were filter-sterilized and boiled prior to transfer to naïve cells to determine transmissibility. Barrier permeability was assessed via transwell assays, cell viability through resazurin, and amyloid burden was monitored with Congo Red and Thioflavin T. Results (if a Case Study enter NA) Kp 1-008 infection induced permeability and tau release from control cells in a dose-dependent manner. Tau and amyloid burden increased over time in supernatants from control PMVECs. Sterile infection supernatants from control cells increased permeability and impaired oxidative metabolism in naïve cells whereas supernatants from tau-/- cells were markedly less pathogenic. Kp 1-008 induced proteinopathic cytotoxicity persisted strongly through two passages when derived from control cells but one passage when produced from tau-/- PMVECs. Conclusion Our results suggest that 1) K. pneumoniae infection of PMVECs generates a lung endothelial-derived proteinopathy and 2) endothelial tau is a significant contributor to its virulence.