Date of Award
Silas J. Leavesley
It is widely known that patients suffer diminished long-term outcomes in the years following secondary infections, infectious diseases that occur during or after treatment of a primary infection such as influenza or COVID-19. One common secondary infection is pneumonia, which has become the most fatal hospital-acquired infection. The bacterium responsible for pneumonia is known as Pseudomonas aeruginosa. The cytotoxic supernatant in these studies was generated from a PA103 strain of Psuedomonas aeruginosa with a type III secretion system that maintains the ability to transfer exoenzymes ExoU and ExoT into target cells during infection. The focus of the following studies was to investigate pathways that contribute to these diminished long-term outcomes for patients. We suggest that there is amyloid mediated disruption of βadrenergic mediated cAMP signaling. Preliminary data indicate that the cytotoxic supernatant produced by P. aeruginosa infection of epithelial cells does not block the βadrenergic receptor well but blocks the prostaglandin receptor well. These data also suggest that the cytotoxic supernatant produced by P. aeruginosa infection of endothelial cells does block the β-adrenergic receptor but does not block the prostaglandin receptor well. Given this preliminary data, we sought to further investigate this discrepancy. We hypothesized that the origin of the cytotoxic supernatant plays a critical role in determining which receptor-mediated signaling pathways are inhibited in response to the cytotoxic supernatant. Results from this study support the notion that the cytotoxic supernatant produced by Pseudomonas aeruginosa infection of epithelial cells does not appear to effectively block the beta-adrenergic receptor type 2 (β2AR) but may block a subset of prostenoid (EP) receptors at the basal surface of the cell. Through these studies we have successfully developed a protocol for screening the effects of cytotoxic supernatant on GPCR pathways.
Tayara, Alia, "Factors Contributing to Diminished Long-Term Outcomes of Secondary Infections" (2021). Undergraduate Theses . 13.