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Investigating the impact of capsule type and capsule-independent determinants of virulence on the burden of pneumococcal disease

Thursday 12 May 2011

Project
Invasive pneumococcal disease causes more than 1.2 million infant deaths per year and a quarter of all preventable deaths in children under 5 years of age. It makes Streptococcus pneumoniae the leading cause of infant mortality worldwide. Pneumococcus is also a commensal of the upper respiratory tract, colonizing the majority of children. The ultimate virulence factor of pneumococcus is the polysaccharide capsule. There are over ninety serotypes of S. pneumoniae described based on capsular polysaccharide chemistry and immunogenicity. The serotype distribution in carriage and disease is not random, and strains of only few capsular types dominate in any given community. The ability of the capsule to induce highly-specific immune responses that protect against disease is utilized in current vaccine strategies, in which capsular sugars are used to induce serotype-specific antibodies against selected serotypes. Immunization with conjugated polysaccharide vaccines (PCVs) has proven highly effective in protecting vaccinated children against disease caused by vaccine-serotypes (VTs), but is also associated with an increase in infections due to non-VTs. This phenomenon is called serotype replacement.

Since there is direct link between distribution of serotypes in disease and circulation in carriage, epidemiological surveillance studies on carriage are a major tool for monitoring the effects of vaccination. Along with surveillances on invasive disease they are used to confirm vaccine effects on VTs and facilitate early detection of new invasive serotypes emerging after PCVs implementation. This allows for the modification of preventive strategies in response to changes in the pneumococcal population, maximising the benefits of vaccination.

Our group combines epidemiological and experimental methods to study the impact of nationwide immunization with pneumococcal vaccines on serotype replacement in pneumococcal disease. We are developing and applying in surveillance studies, new diagnostic methods allowing us to detect earlier and with higher accuracy, any changes in pneumococcal carriage. We combine results of enhanced epidemiological surveillances with experimental in vitro and in in vivo studies to assess virulence of the serotypes emerging in the population of vaccinated hosts. In our work, we heavily rely on genetically manipulated strains. They are utilized to study the possible effect of capsule type and of capsule-independent determinants on strain invasiveness. We aim to identify serotypes, strains or capsule independent factors that contribute most to the burden of pneumococcal disease. This will provide an insight into mechanisms behind the success of a serotype in replacement.

Techniques
general microbiological techniques, in vitro susceptibility assays, polysaccharide expression assays, genetic modification of pneumococcal strains (genes knock-out and cloning), conventional PCR, quantitative PCR, DNA sequencing.

Duration
6 to 9 months

Contact
Dr. Krzysztof Trzcinski, K.Trzcinski@umcutrecht.nl, phone: 088 75 506 27

Key Publications
Li Y, Weinberger DM, Thompson CM, Trzcinski K, Lipsitch M. Surface charge of Streptococcus pneumoniae predicts serotype distribution. Infection and Immunity 2013

Surewaard BGJ, Trzcinski K, Jacobino S, et al. 2013, Pneumococcal immune evasion: ZmpC inhibits neutrophil influx. Cellular Microbiology

Trzcinski K, Bogaert D, Wyllie A, et al. 2013, Superiority of trans-oral over trans-nasal sampling in detecting Streptococcus pneumoniae colonization in adults. PLoS ONE

Hyams C, Trzcinski K, Camberlein E, et al. 2013, Streptococcus pneumoniae capsular serotype invasiveness correlates with the degree of factor H binding and opsonisation with C3b/iC3b. Infection and Immunity

Weinberger DM, Trzcinski K, Lu YJ, et al. 2009, Pneumococcal capsular polysaccharide structure predicts serotype prevalence. PLoS Pathogens

Bogaert D, De Groot R, Hermans PWM (2004) Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infectious Diseases

Trzcinski K, Thompson CM, Lipsitch M. 2003, Construction of otherwise isogenic serotype 6B, 7F, 14 and 19F capsular variants of Streptococcus pneumoniae strain TIGR4. Applied and Environmental Microbiology

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