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You searched for subject:(heme A). Showing records 1 – 3 of 3 total matches.

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Georgia State University

1. Sachla, Ankita J. Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus.

Degree: PhD, Biology, 2015, Georgia State University

Heme is vital to a variety of cellular functions in bacteria ranging from energy generation to iron reserve. Group A streptococcus (GAS) is a prevalent bacterial pathogen that is responsible for an array of human diseases ranging from simple, self-limiting, mucosal and skin infections to invasive and systemic manifestations. GAS needs iron for growth and can satisfy this nutritional requirement by scavenging the metal from heme. The pathogen produces powerful hemolysins that facilitate heme release during infection. Heme is captured and relayed through the GAS cell wall and cytoplasmic membrane by dedicated receptors and transporters. To-date, the fate of the acquired heme is unknown in Streptococci. Although heme is nutritionally beneficial for GAS growth, its pro-oxidant and lipophilic nature makes it a liability with damaging effects on cellular components. The conundrum associated with heme use is particularly pertinent to GAS pathophysiology since invasive GAS infections involve massive hemolysis and the generation of unescorted heme in excess. In this dissertation, I aimed to describe the mechanisms that GAS uses for heme catabolism while managing its toxicity. I conducted a biochemical characterization of a new enzyme, HupZ in GAS that degrades heme in vitro. Similar to the heme oxygenase-1 (HO-1), HupZ activity leads to the formation of iron, CO, and a biliverdin-like product. I also investigated the impact of heme on GAS physiology and identified key mediators in the repair and detoxification process. This study demonstrated that heme exposure leads to a general stress response that involves the activation of antioxidant defense pathways to restore redox balance. Further, I studied a 3-gene cluster, pefRCD (porphyrin-regulated efflux RCD), which was activated by environmental heme, and provided support to my hypothesis that the pefRCD gene encodes a heme-sensing regulator (PefR) and heme efflux system (PefCD). I showed that the pef system protects GAS cells from heme-induced damage to the membrane and DNA by preventing cellular accumulation of heme. In conclusion, this dissertation addresses key knowledge gaps in GAS physiology and provides new insights into heme metabolism of GAS. Advisors/Committee Members: Zehava Eichenbaum, Parjit Kaur, Adam Wilson, Chung-Dar Lu.

Subjects/Keywords: Group A streptococcus; heme toxicity; heme tolerance; PefRCD transporter; heme degradation; HupZ protein

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APA (6th Edition):

Sachla, A. J. (2015). Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus. (Doctoral Dissertation). Georgia State University. Retrieved from https://scholarworks.gsu.edu/biology_diss/159

Chicago Manual of Style (16th Edition):

Sachla, Ankita J. “Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus.” 2015. Doctoral Dissertation, Georgia State University. Accessed October 21, 2020. https://scholarworks.gsu.edu/biology_diss/159.

MLA Handbook (7th Edition):

Sachla, Ankita J. “Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus.” 2015. Web. 21 Oct 2020.

Vancouver:

Sachla AJ. Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus. [Internet] [Doctoral dissertation]. Georgia State University; 2015. [cited 2020 Oct 21]. Available from: https://scholarworks.gsu.edu/biology_diss/159.

Council of Science Editors:

Sachla AJ. Genetic, Biochemical, and Functional Characterization of Heme Metabolism in Group A Streptococcus. [Doctoral Dissertation]. Georgia State University; 2015. Available from: https://scholarworks.gsu.edu/biology_diss/159


University of Alberta

2. Rumley, Alina C. Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase.

Degree: MS, Medical Sciences-Medical Genetics, 2012, University of Alberta

Cytochrome c oxidase (COX) converts oxygen to water as part of oxidative phosphorylation. Studies in yeast estimate that more than forty different genes are required for COX assembly. The heme A prosthetic groups are essential for COX function and defects in heme A synthesis have been shown to underlie human COX deficiencies. The nuclear-encoded Cox15p has been proposed to have a role in heme A synthesis. I have characterized S. cerevisiae cox15 mutant strains with regards to respiratory growth, COX assembly, heme A levels, and stability of the mutant Cox15p. I have identified mutants with a novel phenotype. Initial studies suggest that a cox15 null strain has abnormal mitochondrial morphology and that Cox15p has a role in peroxide metabolism. My results further support the functioning of Cox15p in heme A biosynthesis and provide insight into the variable clinical phenotypes seen in patients with COX15 mutations.

Subjects/Keywords: heme A; Cox15p; cytochrome c oxidase

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APA (6th Edition):

Rumley, A. C. (2012). Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/8s45q984g

Chicago Manual of Style (16th Edition):

Rumley, Alina C. “Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase.” 2012. Masters Thesis, University of Alberta. Accessed October 21, 2020. https://era.library.ualberta.ca/files/8s45q984g.

MLA Handbook (7th Edition):

Rumley, Alina C. “Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase.” 2012. Web. 21 Oct 2020.

Vancouver:

Rumley AC. Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase. [Internet] [Masters thesis]. University of Alberta; 2012. [cited 2020 Oct 21]. Available from: https://era.library.ualberta.ca/files/8s45q984g.

Council of Science Editors:

Rumley AC. Characterization of Cox15p, a cytochrome c oxidase assembly factor and component of the eukaryotic heme A synthase. [Masters Thesis]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/8s45q984g


University of Western Ontario

3. Brozyna, Jeremy R. Iron acquisition strategies employed by Staphylococcus lugdunensis.

Degree: 2016, University of Western Ontario

Iron is crucial for many cellular processes including DNA synthesis and respiration. The majority of iron in mammals is in heme within hemoproteins, inside cells, or transported through circulation by the glycoprotein transferrin, which constitutes the greatest iron source in serum. Limiting iron availability is an important facet of nutritional immunity to help prevent infection. Staphylococcus lugdunensis is a human skin commensal and opportunistic pathogen capable of causing a variety of infections, including particularly aggressive endocarditis. It is an emerging pathogen with elevated virulence compared to other species of coagulase-negative staphylococci. The versatility of S. lugdunensis to infect multiple niches and cause aggressive infection indicates that it likely adapts its cellular physiology to overcome host defenses, including iron limitation. In chapter 2, we demonstrate that, contrary to other staphylococci, S. lugdunensis does not produce a siderophore – small (kDa) iron-chelating molecules that strip iron from host glycoproteins, including transferrin, and deliver it to microorganisms. As such, serum is growth-inhibitory to S. lugdunensis, unless it is supplemented with an iron source. We have identified and characterized several iron-compound transport processes through inactivation of genes required for acquisition of each respective compound. S. lugdunensis transports the staphylococcal carboxylate siderophores staphyloferrin A and staphyloferrin B through Hts and Sir, respectively, and is able to directly appropriate siderophores produced by S. aureus when in coculture, to support its growth. Heme and hemoglobin-iron is acquired via Isd. In chapter 3, we demonstrate that hemolysis enhances growth in blood, in an Isd-dependent manner. An iron-regulated ATPase, FhuC, is required for import of several carboxylate and hydroxamate siderophores, whereas Sst1 transports catecholamine stress hormone-iron (ie. adrenaline, noradrenaline, dopamine). fhuC and sst1 mutants are impaired for growth in absence of hydroxamates and catecholamines, indicating additional substrates acquired by these are vital to S. lugdunensis. Using a novel systemic model of S. lugdunensis infection, we show that a isd fhuC sst mutant is significantly impaired in its ability to colonize internal murine organs, and cause sickness. We have detailed several iron-acquisition systems in S. lugdunensis and are first to show specific transporters are important for pathogenesis in the host.

Subjects/Keywords: Staphylococcus lugdunensis; iron; heme; hemoglobin; siderophores; catecholamine stress hormones; hydroxamates; staphyloferrin A; staphyloferrin B; hemolysis; Bacteriology; Molecular Biology; Molecular Genetics; Pathogenic Microbiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Brozyna, J. R. (2016). Iron acquisition strategies employed by Staphylococcus lugdunensis. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3963

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Brozyna, Jeremy R. “Iron acquisition strategies employed by Staphylococcus lugdunensis.” 2016. Thesis, University of Western Ontario. Accessed October 21, 2020. https://ir.lib.uwo.ca/etd/3963.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Brozyna, Jeremy R. “Iron acquisition strategies employed by Staphylococcus lugdunensis.” 2016. Web. 21 Oct 2020.

Vancouver:

Brozyna JR. Iron acquisition strategies employed by Staphylococcus lugdunensis. [Internet] [Thesis]. University of Western Ontario; 2016. [cited 2020 Oct 21]. Available from: https://ir.lib.uwo.ca/etd/3963.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Brozyna JR. Iron acquisition strategies employed by Staphylococcus lugdunensis. [Thesis]. University of Western Ontario; 2016. Available from: https://ir.lib.uwo.ca/etd/3963

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.