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King, Sam
Streptococcus pneumoniae is a major human pathogen, causing a range of diseases including otitis media, pneumonia, and meningitis. However, S. pneumoniae frequently colonizes the human nasopharynx, asymptomatically. Colonization of the human airway is a necessary precursor for all S. pneumoniae disease. Despite this, the processes by which S. pneumoniae adheres to the human airway, persists, and on occasion progresses to a disease state are poorly understood. The aim of my laboratory is to increase our understanding of the colonization process, with the long term goal of aiding the development of better vaccines or therapeutics. The genetic diversity of S. pneumoniae contributes to the ability of different strains to colonize and cause disease. S. pneumoniae is naturally transformable; meaning that it can take up DNA from the environment. If there is sufficient sequence similarity, recombination can introduce the DNA into the strains genome. This recombination can lead to rapid alterations in bacterial characteristics, for example, the evolution of penicillin resistant S. pneumoniae. There may be a number of ways that this diversity confers a selective advantage for the bacteria, including alterations in enzymatic activities, avoidance of the human immune system, and a reduction in the efficacy of therapeutics and vaccines. Therefore, in addition to establishing the mechanisms of S. pneumoniae colonization and pathogenicity, I am investigating the role and importance that genetic diversity of S. pneumoniae has in affecting these processes. I am currently investigating the bacteria’s ability to deglycosylate human glycoconjugates. S. pneumoniae produces three exoglycosidases (enzymes that cleave specific terminal sugar residues) that act to sequentially deglycosylate many human glycoproteins. Human glycosylation has many important roles, including, cell to cell signaling. We believe that the ability of the bacteria to deglycosylate human glycoconjugates, may contribute, in a number of ways, to the ability of S. pneumoniae to colonize and cause disease. We have recently demonstrated a role for these exoglycosidases in adherence of S. pneumoniae, to human epithelial cells. Therefore, I aim to elucidate this mechanism of adherence from both the bacterial and host sides. In addition, as mutation of the exoglycosidases in another closely related strain shows no reduction in adherence, we can manipulate these different strains to identify other novel mechanisms of adherence. Selected Publications King S. J., Hippe K. R., and Weiser J. N. (2006). Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae. Molecular Microbiology. 59, 961-974 King, S. J., Whatmore, A. M., Dowson, C. G. (2005) NanA, a neuraminidase from Streptococcus pneumoniae, shows high levels of sequence diversity, at least in part through recombination with Streptococcus oralis. Journal of Bacteriology. 187, 5376-86. King S. J., Hippe K. R., Gould J. M., Bae D., Peterson S., Cline R. T., Fasching, C., Janoff E. N., and Weiser J. N. (2004) Phase variable desialylation of host proteins that bind to Streptococcus pneumoniae in vivo and protect the airway. Molecular Microbiology. 54, 159-171 King, S. J., Allen, A. G., Maskell, D. J., Dowson, C.G. and Whatmore, A.M. (2004). Distribution, genetic diversity, and variable expression of the gene encoding hyaluronate lyase within the Streptococcus suis population. Journal of Bacteriology. 186, 4740-4747. Shakhnovich E.A., King S.J. and Weiser, J.N. (2002) Neuraminidase expressed by Streptococcus pneumoniae desialylates the lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: A paradigm for interbacterial competition among pathogens of the human respiratory tract. Infection and Immunity. 70, 7161-7164 King Laboratory Personnel Dominique Limoli Research Assistant Contact Columbus Children's Research Institute Links http://www.microbial-pathogenesis.org/ |
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Sam King, Ph.D. is an Assistant Professor of Pediatrics. She received her Ph.D. from the University Of Warwick, England in 2000 and completed a two year Post-doc at the same institution before completing a 3 year Post-doc at the University of Pennsylvania. She joined the Center for Microbial Pathogenesis at the Columbus Children’s Research Institute in 2005.