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Characterization of Phosphoglycerate Kinase Expressed on the Surface of Group B Streptococcus Open Access


Other title
Phosphoglycerate Kinase
Group B Streptococcus
Type of item
Degree grantor
University of Alberta
Author or creator
Boone, Tyler J
Supervisor and department
Gregory Tyrrell (Laboratory Medicine and Pathology)
Examining committee member and department
Markus Stein (Health Sciences, Albany College of Pharmacy and Health Sciences)
Brenda Leskiw (Biological Sciences, University of Alberta)
Jeffrey Fuller (Laboratory Medicine and Pathology, University of Alberta)
Song Lee (Microbiology and Immunology, Dalhousie University)
Stefan Pukatzki (Medical Microbiology and Immunology, University of Alberta)
Medical Sciences- Laboratory Medicine and Pathology

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Group B streptococcus (GBS) is a major cause of invasive disease in the neonatal and adult populations. To mediate invasive disease, GBS encodes a variety of surface expressed and secreted components. One surface expressed protein that may contribute to GBS virulence is phosphoglycerate kinase (PGK; a glycolytic enzyme). Glycolytic enzymes have been identified on the surface of many Gram positive bacteria, despite the absence of any known secretion or surface attachment signal. My results demonstrate that the SecA2 locus, in particular the Srr1 fimbrial protein, is required for transport of PGK across the GBS membrane. Once across the bacterial membrane, PGK becomes attached to the bacterial surface through interaction with lipoteichoic acid as well as a second ligand that also requires Srr1 for expression. While the surface localization of PGK suggests it may play a role in GBS virulence, confirming their role in virulence has been hampered by its role in glycolysis. Due to the essential cytoplasmic role of PGK in metabolism, traditional knock-out mutagenesis is not possible to determine its function on the bacterial surface. My results demonstrate that GBS-PGK may contribute to GBS virulence through its ability to bind to actin, fibrin, fibrinogen, fibronectin and plasminogen. Site directed mutagenesis, preventing interaction with host proteins without affecting the glycolytic activity, has previously been used to demonstrate a role for the glycolytic enzymes -enolase and glyceraldehyde-3-phosphate dehydrogenase in virulence. Using truncation followed by peptide mapping experiments the actin and plasminogen binding sites of GBS-PGK were located to the amino acids 126-134 and amino acids 302-306. Using site directed mutagenesis, targeting these two locations within the GBS-PGK molecule, I have reduced the actin and plasminogen binding by GBS-PGK without affecting the glycolytic activity. In conclusion, the research presented in this thesis identifies the pathway utilized by GBS-PGK to become surface expressed, identifies potential virulence functions of surface expressed GBS-PGK and identifies mutations within the pgk gene that could prevent these virulence functions without affecting glycolysis. This work contributes to our understanding of surface expressed glycolytic enzymes and should facilitate future research determining the function of surface expressed GBS-PGK.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Verani JR, Schrag SJ. Group B streptococcal disease in infants: Progress in prevention and continued challenges. Clin Perinatol. 2010 Jun;37(2):375-92.Rubens CE, Smith S, Hulse M, Chi EY, van Belle G. Respiratory epithelial cell invasion by group B streptococci. Infect Immun. 1992 Dec;60(12):5157-63.Pancholi V, Chhatwal GS. Housekeeping enzymes as virulence factors for pathogens. Int J Med Microbiol. 2003 Dec;293(6):391-401.Doran KS, Nizet V. Molecular pathogenesis of neonatal group B streptococcal infection: No longer in its infancy. Mol Microbiol. 2004 Oct;54(1):23-31.Soriani M, Santi I, Taddei A, Rappuoli R, Grandi G, Telford JL. Group B streptococcus crosses human epithelial cells by a paracellular route. J Infect Dis. 2006 Jan 15;193(2):241-50.Bergmann S, Rohde M, Chhatwal GS, Hammerschmidt S. Alpha-enolase of streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface. Mol Microbiol. 2001 Jun;40(6):1273-87.Boone TJ, Burnham CA, Tyrrell GJ. Binding of group B streptococcal phosphoglycerate kinase to plasminogen and actin. Microb Pathog. 2011 Jun 28.

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