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

Date
2013-05-03
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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.
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Keywords
Microbiology, Biology--Molecular, Biochemistry, Biology--Molecular
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