Louisiana Research Day Program Book 2025

Biomedical Research: Section 1

Victoria Lucas 1 ; David Kang 1 ; Jedidiah Lim 1 ; Samreen Shah 1 ; Sherine Thomas 1 ; Carlie Christ 1 ; Meredith Gwin, PhD 2 ; Samir Gautam, MD, PhD 2 ; Melissa Lipsmeyer, PhD 1 ; Rebekah Morrow, PhD 3 ; K. Adam Morrow, PhD 1 ; Sarah Voth, PhD 1 *Indicates equal contributions 1 Cell Biology and Physiology, VCOM-Louisiana; 2 Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine; 3 Microbiology and Immunology, Edward Via College of Osteopathic Medicine 22 PSEUDOMONAS INDUCED ARDS PROMOTES CEREBROVASCULAR DAMAGE SECONDARY TO CYSTATIN-C DEPLETION

Background: Nosocomial pneumonia is the most common cause of acute respiratory distress syndrome (ARDS). Despite clearing the Strains responsible for acute infection utilize a type III secretion system (T3SS) to inject toxic exoenzymes directly into host cells. The T3SS toxin expressed by ~ 90% of clinical strains is exoenzyme Y (ExoY). Intoxicated cells are afflicted with tau hyperphosphorylation, cytoskeletal collapse, and the release of pathogenic tau into the extracellular space. In the absence of ExoY-elicited release of cytotoxic tau, endothelial amyloids including amyloid beta (A β ) are cytoprotective, antimicrobial, and contribute to regulation of the coagulation cascade. Cytotoxic tau disrupts the innate function of endothelial amyloids, suppresses antimicrobicity, and may promote cerebral ischemia, a devastating complication of ARDS. Cystatin C (CysC), a ubiquitous cysteine protease inhibitor, plays a pivotal role in amyloid homeostasis. In critically ill patients, blood and urine proteomics indicate that serum CysC is markedly depleted through ARDS-induced inflammatory proteinuria, yet no cause, remedy, or mechanism of this critical care phenomenon has been identified. Here, we hypothesize

that ExoY-mediated pneumonia promotes the formation of cerebral microthrombi and ischemia secondary to the proteinuric depletion of CysC. Methods: Male and female wildtype C57BL/6J mice (10-12 weeks old) were infected intratracheally with either vehicle or 1 x 105 colony forming units (CFU) of bacteria in 40 µl of PBS. P. aeruginosa strain ExoY+ (secretes only ExoY in host cells) was used for infections. Weight and urine were collected daily and survival was tracked. At 48-hours post-infection, surviving mice were sacrificed. Urine was collected via cystocentesis, blood was collected via cardiac puncture, and the brain was fixed for histology. H&E, tetrazolium, and Congo red staining were performed. CysC levels of the blood and urine were measured via ELISA. Amyloid and tau levels were assessed via immunoblotting and thioflavin T.

Biomedical Research: Section 2

Results: TBD

Conclusions: TBD

IN THE PHOTO: Bea Remorca, OMS-II

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2025 Research Recognition Day