Journal
CHEMOTHERAPY
Volume 59, Issue 2, Pages 138-142Publisher
KARGER
DOI: 10.1159/000353439
Keywords
Choline-binding proteins; Streptococcus pneumoniae; Dendrimer; Phagocytosis; Microglia
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Funding
- CAREPNEUMO, European Union [EU-CP223111, BFU2010-17824]
- Sparkasse Gottingen and Dr. Helmut Wagner, Gottingen
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Background: Pneumococcal virulence factors common to all serotypes, such as choline-binding proteins (CBPs), are promising therapeutic targets in pneumococcal infections. We studied the effect of a choline dendrimer with maximized binding affinity/specificity for CBPs on microglia-mediated pneumococcal phagocytosis. Methods: Pneumoccocal cultures were exposed to dendrinners containing 8 choline end groups or amino groups as controls, either from the beginning of bacterial growth or at the late exponential phase. The effect of long/short co-incubation was assessed in terms of bacterial morphological changes and increase in bacterial uptake by primary microglial cultures. Results: Inhibiting CBPs by micronnolar concentrations of a choline dendrimer caused the formation of long pneumococcal chains that were readily phagocytosed by microglia. Enhanced phagocytosis was dendrimer dose-dependent. Long bacteria-dendrimer co-incubation (14 h) resulted in a higher bacterial uptake than short co-incubation (2 h; p < 0.001). Conclusions: Multivalent dendrinners containing choline end groups are promising antimicrobial agents for the management of pneumococcal diseases. (C) 2013 S.Karger AG, Basel
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