Streptococcus pneumoniae research
"Pneumococcus is altogether an amazing cell. Tiny in size, simple in structure, frail in make-up, it possesses physiological functions of great variety, performs biochemical feats of extraordinary intricacy and, attacking man, sets up a stormy disease so often fatal that it must be reckoned as one of the foremost causes of human death."
White B: The Biology of Pneumococcus. New York, The Commonwealth Fund, 1938.
Unfortunately, more than 70 years later the pneumococcus is still, arguably, the most devastating human microbial pathogen (1). It has been estimated by the world health organization that annually 4-5 million people die of pneumonia, two million of which are children, where the majority of deaths occur in developing countries. Streptococcus pneumoniae, aptly named because it is the most important bacterial cause of pneumonia, is likely primarily responsible for these deaths. In addition to causing pneumonia, pneumococcus is also responsible for the 100 000–500 000 deaths from meningitis in children each year. Infections that rarely lead to death include sinusitis and otitis media, the latter one being the second most common disease of childhood after upper respiratory infection in developed countries.
(1) O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, Lee E, Mulholland K, Levine OS, Cherian T. (2009) Lancet; 12;374(9693):893-902
The Veening team is interested in phenotypic bi-stability in Streptococcus pneumoniae and its importance in virulence of this human pathogen.
We are interested in all aspects of transcriptional regulation, including the study of the bacterial cell cycle.
- Streptococcus pneumoniae (the pneumococcus) is a major pathogen causing invasive (pneumonia, meningitis, bacteraemia) and non-invasive (acute otitis media, sinusitis) diseases in young children and in elderly and/or immuno-compromised adults. The last decades have seen the emergence and spread of pneumococcal strains with multiple antibiotic resistance posing a serious threat to human health.
- Within genetically identical populations of bacteria, often only specific subpopulations of cells enter the same developmental pathway and exhibit the same phenotype; a phenomenon known as phenotypic bistability or phenotypic heterogeneity. How populations of genetically identical cells bifurcate into phenotypically distinct subpopulations in the same environment is an important question for developmental biology.
- It is assumed that phenotypic heterogeneity is generated by bacteria as a bet-hedging strategy to ensure that at least some cells within the clonal lineage prevail under fluctuating stressful conditions. Alternatively, phenotypic heterogeneity can act as a ‘division of labour’ process whereby some cells sacrifice themselves to increase the survival chances of its clonal siblings, generate biofilms or successfully colonize its host. Importantly, these mechanisms are often employed by pathogenic bacteria to elude the host immune response, resist antibiotic pressure or invade the host. Obviously, the understanding of differential bacterial development and how bacteria deal with stress is crucial for the control of pathogens.
- Within the Veening team we are interested which molecular mechanism the pneumococcus utilizes to generate phenotypic heterogeneity to aid its survival and proliferation in the host. Using a multidisciplinary approach which includes standard molecular biological techniques, clever genetic screens, DNA-microarrays, Mathematical Modelling, and state of the art single cell techniques such as fluorescence time-lapse microscopy and FACS we try to answer some of these important fundamental questions. Working with S. pneumoniae also requires tool development, for instance see Eberhardt et al, 2009, MolMicro and de Jong et al, 2011, JOVE.