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Investigation Of The Growth And Survival Of Staphylococcus Aureus In Cftr-Deficient Macrophages, Bita Azad
Investigation Of The Growth And Survival Of Staphylococcus Aureus In Cftr-Deficient Macrophages, Bita Azad
Electronic Thesis and Dissertation Repository
Staphylococcus aureus and its small colony variants (SCVs) are commonly isolated from the lungs of cystic fibrosis (CF) patients. Although studies have suggested that cystic fibrosis transmembrane regulator (CFTR)-deficient macrophages are diminished in their ability to kill intracellular pathogens, whether this is true for CFTR-deficient macrophages infected with S. aureus or its SCVs is unknown. I employed gentamicin protection and eFluorÔ-670-based proliferation assays to assess the intracellular replication of S. aureus in CFTR inhibitor treated THP-1 and primary human macrophages, and in primary macrophages derived from CF patient blood. My work shows that the susceptibility of CFTR-deficient macrophages to the …
The Surreptitious Survival Of The Emerging Pathogen Staphylococcus Lugdunensis In Macrophages Enhances S. Aureus Infection, David Watson
The Surreptitious Survival Of The Emerging Pathogen Staphylococcus Lugdunensis In Macrophages Enhances S. Aureus Infection, David Watson
Electronic Thesis and Dissertation Repository
Staphylococcus lugdunensis is an opportunistic pathogen that can cause invasive infections suggesting an ability to circumvent host immunity. S. lugdunensis was shown to resist killing and persist within macrophages and acetylation of its peptidoglycan is important for this survival. This was consistent in vivo, as S. lugdunensis resides inside Kupffer cells for at least 16 hours post-infection in mice. Despite its capability for survival, S. lugdunensis is unable to replicate within phagolysosomes. Inhibiting phagolysosomal effectors allows S. lugdunensis to initiate replication, after which the bacteria escape phagosomal containment. Moreover, intracellular S. lugdunensis augments the growth S. aureus during co-infection. Eight …
Iron And Copper Homeostasis In Staphylococcus Aureus, Holly A. Laakso
Iron And Copper Homeostasis In Staphylococcus Aureus, Holly A. Laakso
Electronic Thesis and Dissertation Repository
All microorganisms require transition metals for key metabolic processes, thus during infection microbial access to essential metals is tightly regulated by the host in a process termed nutritional immunity. Iron acquisition is critical to the pathogenesis of the formidable human pathogen, Staphylococcus aureus, which utilizes heme-uptake systems and two high-affinity iron-scavenging siderophores, staphyloferrin A (SA) and staphyloferrin B (SB) for iron acquisition. In this study, I identify sbnI as encoding a transcription factor required for expression of genes in the sbn operon, the biosynthetic operon for SB synthesis. I also show that SbnI is a novel hemoprotein, where binding …
The Intracellular Behaviour Of Burkholderia Cenocepacia In Murine Macrophages, Jennifer S. Tolman
The Intracellular Behaviour Of Burkholderia Cenocepacia In Murine Macrophages, Jennifer S. Tolman
Electronic Thesis and Dissertation Repository
Burkholderia cenocepacia is an opportunistic pathogen causing life-threatening infections in cystic fibrosis and other immunocompromised patients. The bacterium survives within macrophages by interfering with typical endocytic trafficking, resulting in delayed maturation of a B. cenocepacia-containing phagosome. We hypothesize that B. cenocepacia alters gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation. Furthermore, we hypothesize that specialized bacterial secretion systems are involved in the interactions between intracellular bacteria and macrophages. In this work, we characterize later-stage infection of macrophages by B. cenocepacia, showing replication within an acidified endosomal compartment suggestive of a phagolysosome. …