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dc.contributor.authorLiu, Xinyanen_US
dc.date.accessioned2019-08-19T12:13:13Z
dc.date.issued2005
dc.date.submitted2005
dc.identifier.otherb25938277
dc.identifier.urihttps://hdl.handle.net/2144/37164
dc.descriptionThesis (Ph.D.)--Boston University, Henry M. Goldman School of Dental Medicine.en_US
dc.descriptionPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.en_US
dc.description.abstractPorphyromonas gingivalis , a Gram-negative anaerobic pathogen of periodontal diseases, requires iron in the form of heme (a term used to denote either the ferrous or ferric form of iron protoporphyrin IX) for growth. P. gingivalis is capable of utilizing a broad range of heme-containing compounds such as hemoglobin, hemoglobin-bound haptoglobin, hemin-bound hemopexin and hemin-saturated serum. Heme and hemoglobin utilization in P. gingivalis requires the participation of an outer membrane protein HmuR (heme utilization receptor), as well as cysteine proteinase gingipains (Lysine-specific gingipain Kgp and Arginine specific gingipains Rgps). However, the specific mechanisms utilized for heme acquisition are poorly understood. In this study, the role of HmuR in heme utilization was characterized in both E. coli and P. gingivalis . Molecular interaction between HmuR and hemin/hemoproteins was also characterized by construction and analysis of HmuR site-directed mutants. Our results support the direct role of HmuR in heme utilization. Hemoprotein utilization in P. gingivalis requires the participation of HmuR conserved residues. The HmuR residues 95 and 434, as well as the NPDL motif, seem to be involved in whole cell binding of hemoproteins; while the YRAP motif does not. All these residues seem essential for serum hemoprotein utilization. Analyses of HmuR by homology modeling provided a structural basis for functional analysis and supported the results from mutagenesis studies. In addition, expression of the hmuR, kgp and rgpA genes in response to different heme sources was also examined. We found that expression of the hmuR gene was negatively regulated by heme, while expression of the kgp and rgpA genes seemed to be regulated by growth phase. These different regulatory mechanisms, as well as the coordinate expression between HmuR and gingipains, indicate a complementary regulation mechanism for optimal heme utilization in P. gingivalis.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.subjectPeriodontologyen_US
dc.subjectOral biologyen_US
dc.subjectMicrobiologyen_US
dc.subjectPorphyromonas gingivalisen_US
dc.subjectDental medicineen_US
dc.titleMolecular characterization of Porphyromonas gingivalis heme utilization systems--role of HmuR and gingipains in heme utilizationen_US
dc.typeThesis/Dissertationen_US
dc.description.embargo2031-01-01
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplinePeriodontologyen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.barcode11719022869145
dc.identifier.mmsid99192042360001161


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