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dc.contributor.authorPi, Hualiang
dc.date.accessioned2018-10-23T13:22:43Z
dc.date.available2019-06-04T06:02:11Z
dc.date.issued2018-05-30
dc.identifier.otherPi_cornellgrad_0058F_10706
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:10706
dc.identifier.otherbibid: 10489503
dc.identifier.urihttps://hdl.handle.net/1813/59418
dc.description.abstractIron is required for most bacteria but its bioavailability is extremely low. So iron acquisition has become a major challenge in bacterial physiology. Iron acquisition includes uptake systems for elemental iron, ferric citrate, and various ferric-siderophore complexes. Iron-mediated regulation takes place at multi-levels: transcriptional, post-transcriptional, and translational. These regulatory systems enable bacteria to achieve homeostatic balance with iron (Chapter 1). Iron is also toxic at elevated levels. Recent results revealed that Fe(II) exporters play a crucial role in preventing iron overload. These include P1B-type ATPases, cation diffusion facilitators, major facilitator superfamily proteins, and membrane bound ferritin-like proteins (Chapter 2). Among these systems, FrvA is a virulence factor in Listeria monocytogenes. The characterization of FrvA as an Fe(II) efflux transporter provides the first direct evidence linking iron efflux to bacterial pathogenesis. Furthermore, FrvA is a high-affinity Fe(II) exporter and its expression imposes severe iron starvation in Bacillus subtilis (Chapter 3). Thus it has been employed as an inducible genetic tool to study iron limitation responses. Iron acquisition and homeostasis systems need to be tightly regulated to ensure sufficiency for biological functions but not excess that would trigger intoxication. The ferric uptake regulator (Fur) monitors intracellular iron levels and plays a central role in maintaining bacterial iron homeostasis. However, it is unclear whether Fur-regulated genes are derepressed coordinately or in a sequential manner upon iron starvation. Here the iron limitation responses were characterized in B. subtilis (Chapter 4). In particular, the Fur-regulated genes are induced in three sequential waves in response to iron depletion: (i) cells increase their capacity for iron import from common sources of iron in the environment; (ii) cells turn on high-affinity siderophore-mediated import systems to scavenge iron; (iii) as iron levels decrease further, cells activate an iron-sparing response to remodel their proteome. This graded response correlates with in vivo occupancy of Fur protein and can be explained, at least in part, as a direct effect of differences in operator binding affinity of Fur protein. These results provide insights into the distinct roles of Fur-target genes and contribute to our understanding of bacterial metalloregulatory systems.
dc.language.isoen_US
dc.subjectBiochemistry
dc.subjectGenetics
dc.subjectbacterial pathogenesis
dc.subjectferrous iron efflux
dc.subjectFur regulon
dc.subjectgraded response
dc.subjectiron limitation
dc.subjectiron-sparing response
dc.subjectMicrobiology
dc.titleIRON HOMEOSTATIC SYSTEMS AND IRON LIMITATION RESPONSES IN BACTERIA
dc.typedissertation or thesis
thesis.degree.disciplineMicrobiology
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Microbiology
dc.contributor.chairHelmann, John D.
dc.contributor.committeeMemberPeters, Joseph E.
dc.contributor.committeeMemberKe, Ailong
dcterms.licensehttps://hdl.handle.net/1813/59810
dc.identifier.doihttps://doi.org/10.7298/X49Z9345


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