Date of Award
Co-Chairs: Terrence J. Ravine and Phoibe Renema
Robin J. Mockett and Troy Stevens
P. aeruginosa is the most common cause of ventilator-associated pneumonia in ICU patients. P. aeruginosa uses a type III secretion system to inject exoenzymes S, T, U, and Y into host cells, exhibiting unique effects. Pulmonary microvascular endothelial cells (PMVECs) are used to evaluate cellular changes caused by exoenzymes. ExoY infection of PMVECs leads to cell rounding but does not lead to cell death, unlike ExoS/T. The current study evaluated the exoenzyme-induced modulation of intrinsic apoptosis in endothelial cells. Strain PAK, producing ExoS, T, and Y, was compared to isogenic strains expressing either S, SY, T, TY, Y, or none (Ø). PMVECs were infected with either wild type (STY) or isogenic strains. Post-infection, cell morphology, LDH release, cytochrome C levels, and Bcl-xL levels were assessed. LDH results demonstrated ExoY does not inhibit ExoS/T-mediated cell death in PMVECs. Results indicated PAK isogenic strain infections of PMVECs do not affect Bcl-xL expression. Results suggested ExoY inhibits ExoT-induced cytochrome C release, and ExoS-induced LDH release does not occur via the intrinsic pathway. We report that infection with P. aeruginosa ExoS, T and Y leads to distinct differences in cell morphology, signaling, and death in PMVECs.
Vavrinek, Andrea M., "Role of Pseudomonas aeruginosa Exoenzymes S, T, and Y in the Modulation of Intrinsic Apoptosis in Pulmonary Microvascular Endothelial Cells" (2023). Undergraduate Theses. 35.