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Doctor of Philosophy


Microbiology and Immunology


Dr. John McCormick


Streptococcus pyogenes is a Gram-positive, human-specific bacterial pathogen with the ability to cause a wide range of diseases from strep throat to necrotizing fasciitis and toxic shock syndrome. In addition, S. pyogenes may also induce post-streptococcal sequelae including rheumatic fever, acute glomerulonephritis, and reactive arthritis. Although primarily recognized as a pathogen, S. pyogenes also colonizes the skin and throat often without causing disease, and while numerous surface adhesions are important to attach to these surfaces, additional factors important for colonization and persistence by S. pyogenes are poorly understood. In addition to host defence mechanisms, the upper respiratory tract also contains other endogenous microorganisms that compete for the same niche. In order to gain a more complete understanding as to how S. pyogenes is able to adapt within the nasopharyngeal environment, a recombinase-based in vivo expression technology (RIVET) system was developed to identify genes activated in the nasopharyngeal niche using a humanized murine model. Using RIVET, 82 unique clones were recovered revealing 22 ‘cryptic’, 9 ‘typical’, and 30 ‘antisense’ in vivo induced promoters with single inserts. One ‘typical’ promoter (Pblp) that controlled a putative class IIb bacteriocin operon was further characterized. Testing this promoter as a single clone in the RIVET system confirmed its activation in vivo. However, in vitro testing failed to activate this bacteriocin, despite continued addition of the characterized pheromone, SilCR. A blp operon deletion was out-competed by the wild-type S. pyogenes in vivo, but not in vitro. Activation of the bacteriocin in vivo provides a further explanation for the ability of S. pyogenes to occupy the nasopharyngeal niche and begin the process of colonization. This work provides a new molecular tool for the in vivo analysis of S. pyogenes, and demonstrates a novel bacteriocin system important for niche adaptation by S. pyogenes.

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