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Jan-Willem Veening Molecular Genetics Department j.w.veening@rug.nl http://molgen.biol.rug.nl

Development of new tools to study the cell biology and origins of phenotypic variation in the human pathogen Streptococcus pneumoniae : An overview of recently started projects and future directions. Jan-Willem Veening Molecular Genetics Department j.w.veening@rug.nl http://molgen.biol.rug.nl.

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Jan-Willem Veening Molecular Genetics Department j.w.veening@rug.nl http://molgen.biol.rug.nl

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  1. Development of new tools to study the cell biology and origins of phenotypic variation in the human pathogen Streptococcus pneumoniae:An overview of recently started projects and future directions Jan-Willem Veening Molecular Genetics Department j.w.veening@rug.nl http://molgen.biol.rug.nl

  2. Why study Streptococcus pneumoniae? • Human pathogen • Causes e.g. pneumoniae, otitis media, septicaemia, meningitis • Every year >106 deaths worldwide • Transient commensal in ~40% of human population • Resides in nasopharynx • >90 different capsule types • Capsule-polysaccharide vaccination • Vaccine against 23 serotypes • Treatment with antibiotics

  3. Why study Streptococcus pneumoniae? threats: Displacement of vaccine serotypes by other serotypes Invasive disease caused by non-vaccine serotypes Increased antibiotic resistance

  4. Why study Streptococcus pneumoniae? future: Development of protein vaccines and new antimicrobials Need for protein targets that are essential and common in most strains But… cell biology is poorly understood

  5. Why study Streptococcus pneumoniae? • S. pneumoniae needs acomplex regulatory network to regulate host-pathogen interactions • Makes a switch from commensal to pathogen • A common mechanism to elude stresses such as antibiotic stress, immune response stress or to invade the host is by cellular differentiation of a fraction of the clonal population. This heterogeneity can originate from noise that arises during the process of transcription • Phenotypic variation! • Mechanisms poorly understood • Compact genome of about 2 MB • only two sigma factors • Genetically accessible • Naturally competent for transformation • Use of linear DNA (e.g. PCR products) • Single cell analysis toolbox starting to become available

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