Regulatory responses of Streptococcus pneumoniae to varying metal ion- and nitrogen availability

Streptococcus pneumoniae, also pneumococcus, is one of the most feared bacterial pathogens in humans. There is a big research effort aiming at the development of effective and cheap vaccines against this bacterium. This requires proper knowledge of factors that enable S. pneumoniae to cause infection, so-called virulence genes. This thesis describes the development of techniques to study pneumococcus at the molecular level, most importantly a method to screen the entire genome for virulence genes. Besides, the transcriptional response of S. pneumoniae to two external factors, metal ion- and nitrogen availability, was investigated. It turns out that manganese and zinc strongly affect the expression of a number of virulence genes, for which three metal-sensitive regulatory proteins are shown to be responsible. The concentrations of manganese and zinc in the different sites in the human body vary greatly and this could be a signal for S. pneumoniae to adapt the expression pattern of its virulence genes. Furthermore, S. pneumoniae has a generally existing system to be able to efficiently make use of glutamate and glutamine, the two most important amino acids. The different components of this system influence virulence in different body tissues. Moreover, elimination of both glutamine uptake and -synthesis renders S. pneumoniae totally avirulent. The results contribute to the understanding of the molecular biology of pneumococcus, which is of importance for the development of improved strategies to prevent infection with this bacterium.

	Title and contents
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	References
	Samenvatting
	List of publications
	Dankwoord
	Volledige dissertatie

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