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Understanding the relationship between central metabolism and virulence in the human pathogen Streptococcus pneumoniae
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Resumo(s)
Streptococcus pneumoniae is a normal inhabitant of the human
nasopharynx, but it is better known for its role in a plethora of human diseases.
Growing emergence of antibiotic-resistant streptococci and non-type vaccine
strains increases the urgency of finding new targets for the development of novel
therapeutic and preventive drugs. As a major concern for global public health,
S. pneumoniae has always attracted great attention from the scientific community,
which has translated into knowledge on pathogenesis and virulence and the
development of a considerable “toolbox” for genetic manipulation and genomic
analysis, as well as a large number of deciphered genome sequences.
Interestingly, genome-wide studies have consistently pinpointed genes involved in
carbohydrate uptake and metabolism as essential for the virulence of
S. pneumoniae. These global studies offered the opportunity to investigate in
greater depth the potential connections between basic physiology, and in
particular central metabolism, and pneumococcal virulence and pathogenesis.
The general goal of this thesis is to achieve a deeper understanding of the
molecular mechanisms underlying sugar metabolism and their relation to
virulence factors in S. pneumoniae, with a special focus on capsule production. In
the present work, glucose (Glc) and galactose (Gal) were used as carbon sources
for the study of pneumococcal sugar metabolism. This choice was made for two
reasons: Firstly, Glc is a common preferred sugar and is also found as a major
carbon source in niches potentially occupied by S. pneumoniae during host
inflammation or hyperglycaemia. Secondly, Gal, generally a slowly metabolized
non-preferred sugar, is a major carbohydrate in the human nasopharynx, the
non-pathological colonization niche of S. pneumoniae.
Descrição
Dissertation presented to obtain the Ph.D. degree in Biochemistry
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Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica