Phenotypic and Genotypic Models of Streptococcal Colonization of the Human Tonsil

Author

Dennis J. Spencer

Date of Award

2013

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Fischetti Laboratory

Abstract

Pharyngitis due to oropharyngeal infection with Streptococcus pyogenes is most commonly treated by using penicillin-derived antibiotics.While treatment failure in the 1950’s was reported in 4-8% of children, more recent studies have alarmingly found antibiotic failure as high as 20-40% providing the impetus to study this important pathogen. The contiguous mucosa along neighboring oropharyngeal surfaces is classically unaffected during Strep ”Throat” suggesting pathogen specificity for palatine tonsil epithelium. While recent studies are advancing the premise of pathogen-host microenvironment effects on streptococcal virulence, the specific interaction between S. pyogenes and the human tonsillar surface relative to neighboring tissues remains insufficiently understood. This thesis investigates the unique interaction between the Group A Streptococcus, GrAS, and the human tonsil surface. We were particularly interested in the transcriptional response exhibited by the bacterium during coculture with this tissue epithelium compared to epithelium from an anatomically neighboring sight to determine if phenotype might be informed by the genotypic profile. During the course of this work, we introduce new palatine tonsil tumorderived cell lines for their novel usefulness as a model for studying pharyngitis. Using primary tonsil epithelial cells from non-malignant patient samples to confirm our studies with the cancer cell line, we were successful in demonstrating a tissue-specific phenotype and have begun the process of elucidating the genotypic nuances that an M1 strain exhibited in direct response to the tonsillar environment. These and further studies should allow us to better understand the pathogenic adaptions exhibited by this bacterium at its preferred target niche for infection.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Spencer, Dennis J., "Phenotypic and Genotypic Models of Streptococcal Colonization of the Human Tonsil" (2013). Student Theses and Dissertations. 226.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/226