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Title: Streptococcus pneumoniae : involvement of neuraminidase, autolysin and superoxide dismutase in respiratory tract infections
Author: Da Cruz Manco, Sonia
ISNI:       0000 0004 2697 6730
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2010
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This study focuses on the Streptococcus pneumoniae virulence factors neuraminidases A and B, autolysin and superoxide dismutase, with the aim of improved understanding of their roles in the pneumococcal infections. Understanding the pathogenesis of pneumococcal infection is important because this bacterium is one of the most common bacterial causes of human disease and death and because of the emergence of multidrug-resistant strains and issues with the current vaccines. Using a murine model of bronchopneumonia it was shown that NanA and NanB have involvement in colonisation of the upper respiratory tract and in systemic spread. Lack of either of these proteins enhanced bacterial clearance in the nasopharynx, lungs and blood. Furthermore, this study demonstrated distinct roles for each of the neuraminidases, but also suggests synergistic action. Infection data clearly show that the absence of one neuraminidase is not compensated by the presence of the other. This study identified, for the first time, a role for NanB in pathogenesis and in multiplication at mucosal sites. The major S. pneumoniae autolysin LytA has been implicated in pathogenicity by releasing virulence factors and components of the cell wall. In this study, the avirulence of a pneumococcal autolysin-deficient mutant was confirmed. Moreover, the results show that early after infection, LytA is crucial to pneumococcal survival and growth, both in the upper and lower respiratory tract. The major pneumococcal enzyme for detoxifying superoxide is MnSOD, encoded by sodA. This study showed that absence of sodA impaired survival in the respiratory tract, particularly early after infection, but its absence was not lethal, suggesting that other mechanisms are involved in superoxide detoxification.
Supervisor: Andrew, P. Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available