Stress response proteins in Streptococcus pneumoniae

Ibrahim, Yasser Musa (2004) Stress response proteins in Streptococcus pneumoniae. PhD thesis, University of Glasgow.

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Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b2243401

Abstract

Streptococcus pneumoniae (the pneumococcus) is a bacterial pathogen that continues to be associated with considerable morbidity and mortality worldwide. The infection process exposes the pneumococcus to numerous stress conditions, including temperature shift between the upper respiratory tract and deeper tissues, pH changes, exposure to reactive oxygen species generated by host phagocytes, and nutritional deprivation. This thesis aimed at the investigation of the role of the stress response in the virulence process. The functions of caseinolytic protease specificity subunit, ClpC and the protease subunit, ClpP were investigated as an example of ATP-dependent proteases, hi addition, the role of the high temperature requirement A protein, HtrA, which is an example of the ATP-independent proteases, was also studied. Mutants lacking these proteins were constructed in different genetic backgrounds and their phenotypes were compared to the wild types both in vitro and in vivo. ClpC was found to contribute to autolysis of the pneumococcus in a strain-dependent manner. ClpC was required for the release of autolysin A and pneumolysin in serotype 2 S. pneumoniae strain D39. In vivo, ClpC was required for the growth of the pneumococcus in the lungs and blood in a murine model of disease but it does not affect the overall outcome of pneumococcal disease. This thesis also reports the requirement of ClpP for the growth at elevated temperature and virulence of serotype 4 strain, TIGR4 and confirms its contribution to the thermotolerance, oxidative stress resistance and virulence of D39. Data also revealed that HtrA is a key viralence factor of S. pneumoniae. The virulence of ΔhtrA mutants were completely abolished (type 2) or significantly reduced (type 4) in mouse pneumonia and bacteraemia models. HtrA was involved in the ability of the pneumococcus to grow at higher temperatures, to resist oxidative stress and to undergo genetic transformation. Furthermore, the regulation of virulence by the two-component system CiaR/H was found to be mediated through HtrA. Further analysis of ΔhtrA mutants by proteomics and microarray is also shown in this thesis.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Mitchell, Prof. Tim
Date of Award: 2004
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:2004-74286
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jul 2019 14:09
Last Modified: 15 Aug 2019 15:55
URI: http://theses.gla.ac.uk/id/eprint/74286
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