The Role of Lactoferrin Binding Protein B in Gram-Negative Pathogens

Morgenthau, Ari Stephen

The Role of Lactoferrin Binding Protein B in Gram-Negative Pathogens

atmire.migration.oldid	962
dc.contributor.advisor	Schryvers, Anthony
dc.contributor.author	Morgenthau, Ari Stephen
dc.date.accessioned	2013-05-03T21:33:59Z
dc.date.available	2013-06-10T07:00:47Z
dc.date.issued	2013-05-03
dc.date.submitted	2013	en
dc.description.abstract	The human pathogens Neisseria meningitidis and N. gonorrhoeae express a receptor capable of binding to, and removing iron from, the host glycoprotein lactoferrin. Similar to the transferrin binding protein complex, the lactoferrin receptor consists of an integral outer membrane protein, lactoferrin binding protein A (LbpA), and a surface exposed bi-lobed lipoprotein, lactoferrin binding protein B (LbpB). Human gonococcal infection models have shown that possession of either lactoferrin or transferrin binding proteins are essential for survival, while possession of both receptors provides a competitive advantage during co-infection. This thesis identifies a novel function for LbpB showing that LbpB is capable of providing protection against human lactoferricin, a short cationic peptide derived from human lactoferrin. It further demonstrates that the protection by LbpB is mediated by two clusters of negatively charged amino acids that localize to exposed loops in the C-terminal lobe of LbpB, a region with no previously experimentally demonstrated function. In addition, this thesis demonstrates that the protection provided by LbpB in our assay system is underestimated, due to the activity of NalP, an outer membrane protein mediating proteolytic release of LbpB from the surface. An isogenic mutant lacking NalP activity has substantially enhanced protection in our assay, which is likely more representative of the activity of LbpB in vivo. In this study the negatively charged capsular polysaccharide is shown to confer a modest degree of protection against lactoferricin at lower concentrations of lactoferricin. This thesis also includes preliminary experiments demonstrating that protection mediated by LbpB can extend to other cationic antimicrobial peptides. Thus this study indicates that LbpB provides substantial protection against the antimicrobial peptide derived from human lactoferrin and may provide effective protection against similar elements of the innate host defense mechanisms.	en_US
dc.identifier.citation	Morgenthau, A. S. (2013). The Role of Lactoferrin Binding Protein B in Gram-Negative Pathogens (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28329	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/28329
dc.identifier.uri	http://hdl.handle.net/11023/699
dc.language.iso	eng
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary	en
dc.publisher.place	Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Microbiology
dc.subject	Biology--Molecular
dc.subject	Biochemistry
dc.subject	Biology--Molecular
dc.subject.classification	Lactoferrin	en_US
dc.subject.classification	Lactoferrin binding protein B	en_US
dc.subject.classification	Lactoferricin	en_US
dc.subject.classification	LbpB	en_US
dc.subject.classification	Antimicrobial peptides	en_US
dc.subject.classification	cationic antimicrobial peptides	en_US
dc.subject.classification	Neisseria	en_US
dc.title	The Role of Lactoferrin Binding Protein B in Gram-Negative Pathogens
dc.type	master thesis
thesis.degree.discipline	Microbiology & Infectious Diseases
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.item.requestcopy	true