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Title: Modelling nasopharyngeal colonisation by Streptococcus pyogenes : bioluminescence and other longitudinal techniques
Author: Alam, Faraz Mainul
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Streptococcus pyogenes causes an estimated 616 million pharyngitis cases per year and a variety of invasive diseases such as necrotising fasciitis and toxic shock syndrome. The human nasopharynx is the major reservoir for all S. pyogenes infection, including severe invasive disease. A combination of biophotonic imaging (BPI) and direct nasal sampling techniques were used to longitudinally measure the in vivo carriage of S. pyogenes, looking at the effects of virulence factor expression on carriage and transmission and to enable vaccine evaluation. Direct nasal sampling demonstrated that the two component regulatory system, CovR/S, is required for infection and transmission from the nasopharynx. The fitness cost conferred by covR/S mutation in the nasopharynx may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite conferring a selective advantage in invasive infection. Bioluminescent S. pyogenes strains expressing the luxABCDE operon demonstrated a growth deficit independent of the target site for integration in vitro that manifested as a fitness cost during infection in vivo. Notwithstanding this, bioluminescence expression permitted longitudinal quantitation of S. pyogenes within the nasopharynx using BPI. Intramuscular vaccination with heat killed streptococci or the streptococcal chemokine protease SpyCEP conferred protection against pharyngeal infection in this model. These longitudinal techniques allow for S. pyogenes to be tracked in the nasopharynx non-invasively, and allow for new insights into the pathogenesis of this disease.
Supervisor: Sriskandan, Shiranee ; Wiles, Siouxsie Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available