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Noise in gene expression as a determinant of virulence of the human pathogen Streptococcus pneumoniae

Final Report Summary - PNEUMOCELL (Noise in gene expression as a determinant of virulence of the human pathogen Streptococcus pneumoniae)

Streptococcus pneumoniae (pneumococcus) is yearly responsible for more than a million deaths by causing septicemia, meningitis and pneumonia. How the interaction of this bacterium with its human host changes pneumococcus from being benign to causing disease is poorly understood. The main hypothesis of this project is that random fluctuations in gene expression (noise) trigger phenotypic changes in the pneumococcus, which in its turn initiates disease. In this ERC project, we have developed a suite of new genetic and single cell analytical techniques for use in S. pneumoniae. At the same time, we have mapped the transcriptional changes that occur during pneumococcal infection in both host and bacterium. This showed global rewiring of the transcriptomes of both host and pathogen. High-end microscopy revealed large cell-to-cell variability of both host and pneumococcus during infection. Using synthetic and systems biology approaches the Veening laboratory will now test whether heterogeneity in gene expression of both host and S. pneumoniae is important for virulence.