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Pathogenic Microbiology Commons

Open Access. Powered by Scholars. Published by Universities.®

2018

Theses and Dissertations

Articles 1 - 2 of 2

Full-Text Articles in Pathogenic Microbiology

Orientia Tsutsugamushi Modulates Endoplasmic Reticulum Stress To Benefit Its Intracellular Growth And Targets Nlrc5 To Inhibit Major Histocompatibility Complex I Expression, Kyle G. Rodino Jan 2018

Orientia Tsutsugamushi Modulates Endoplasmic Reticulum Stress To Benefit Its Intracellular Growth And Targets Nlrc5 To Inhibit Major Histocompatibility Complex I Expression, Kyle G. Rodino

Theses and Dissertations

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, afflicts one million people annually. Despite being a global health threat, little is known about O. tsutsugamushi pathogenesis. Here, we demonstrate that O. tsutsugamushi modulates the ER and ER-associated processes as mechanisms of nutritional virulence and immune evasion. To obtain amino acids to fuel replication, O. tsutsugamushi simultaneously induces ER stress and the unfolded protein response (UPR) while inhibiting ER-associated degradation (ERAD) during early infection time points. During exponential growth, the bacterium releases the ER bottleneck, resulting in generation of ERAD-derived amino acids that it parasitized for replication. …


Acid Sphingomyelinase Is Essential For Vacuolar Development Of A. Phagocytophilum., Chelsea Cockburn Jan 2018

Acid Sphingomyelinase Is Essential For Vacuolar Development Of A. Phagocytophilum., Chelsea Cockburn

Theses and Dissertations

Obligate intracellular bacteria are significant causes of morbidity and mortality with over two hundred and fifty million infections worldwide annually. One such bacterium, Anaplasma phagocytophilum is the etiologic agent of human granulocytic anaplasmosis (HGA), a tick-transmitted febrile illness. Previous studies have shown that A. phagocytophilum lacks genes for cholesterol biosynthesis and solely relies on Niemann Pick protein type C (NPC)1-mediated low density lipoprotein (LDL)-derived cholesterol to complete its infection cycle.Acid sphingomyelinase (ASMase) is a lysosomal enzyme that is essential for diverse cellular processes including liberation of LDL-derived cholesterol from the lysosome. By first studying A. phagocytophilum, we found that …