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
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
Why study Streptococcus pneumoniae?
threats:
Displacement of vaccine serotypes by other
serotypes
Invasive disease caused by non-vaccine serotypes
Increased antibiotic resistance
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
Why study Streptococcus pneumoniae?
•
S. pneumoniae needs a complex 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
•
•
•
Compact genome of about 2 MB
–
•
only two sigma factors
Genetically accessible
–
–
•
Phenotypic variation!
Mechanisms poorly understood
Naturally competent for transformation
Use of linear DNA (e.g. PCR products)
Single cell analysis toolbox starting to become available