Persistence in Streptococcus pneumoniae infections: elucidation of the importance of persister cells in chronic and recurrent infections

Streptococcus pneumoniae is an important human pathogen, as it is one of the most common causes of community-acquired pneumonia and otitis media. Several issues arise when battling these infections. First, replacement of vaccine-serotypes by new ones has been observed. Second, antibiotic resistance is an emerging problem. Also, antibiotic persistence is considered an important, yet underexposed phenomenon. Persister cells are a subpopulation of cells that are tolerant to lethal concentrations of antibiotics and are involved in a variety of chronic and recurrent infections. However, little to nothing is known about persister formation in S. pneumoniae. This project aims to fill this gap in knowledge. As in vitro autolysis hampers the prolonged monitoring of cultures, a variety of strategies – including the generation of mutant strains – will be applied to overcome this issue. Using heritability assays and gene sequencing to exclude arising of antimicrobial resistance, the presence of persisters will be confirmed. Furthermore, an in vivo model for persister studies will be optimized to confirm the clinical relevance of in vitro results. Lastly, the propensity to form persisters, the antimicrobial susceptibility profile, the strain origin and the in vivo virulence of a set of 50 clinical isolates will be evaluated. Collectively, this project will significantly progress our understanding of importance of persisters in the pathology of S. pneumoniae infections.

Keywords:STREPTOCOCCUS PNEUMONIAE, ANIMAL MODELS, BACTERIOLOGY

Disciplines:Bacteriology

Project type:Collaboration project