- Bacterial genetics in meningitis: Associating meningococcal and pneumococcal genes with clinical outcome
D. van de Beek
A. van der Ende
- Award date
- 22 June 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The objective of this thesis is to provide more insight in the association of bacterial genetics with clinical characteristics of patients with bacterial meningitis. In a genetic association study using a cohort of 258 meningococcal meningitis patients, we show that specific meningococcal clonal complexes, meningococcal factor H binding protein (fHbp) types and meningococcal two-partner secretion system distribution are associated with clinical outcome. In a study contributing to vaccine research, we describe the genetic distribution of the 3 meningococcal antigens that are included in the serogroup B meningococcal vaccine in meningococcal isolates collected in the Netherlands over a period of 50 years. We report the availability of the N. meningitidis serogroup B H44/76 genome sequence, a strain widely used in molecular genetics studies. Also we analyze the genome of a clinical meningococcal meningitis isolate without lipopolysaccharide (LPS) and show that a mutation located in lpxH, which encodes an enzyme in the lipid A biosynthesis pathway, explains its LPS-deficiency. Finally we identified pneumococcal arginine biosynthesis genes to be associated with clinical outcome in patients with pneumococcal meningitis, using a clinical phenotype-based approach combined with bacterial whole-genome sequencing. This thesis, in which more than half of our analyses are based on newly sequenced bacterial whole genome sequences, serves as a proof of principle that bacterial whole-genome sequencing can give answers to research questions that previously remained unanswered. This thesis has contributed to a better understanding of the role of bacterial genetics in the clinical course and outcome of bacterial meningitis.
- Research conducted at: Universiteit van Amsterdam
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