Multivalent choline dendrimers increase phagocytosis of Streptococcus pneumoniae R6 by microglial cells.
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 dendrimers 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 micromolar 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 dendrimers containing choline end groups are promising antimicrobial agents for the management of pneumococcal diseases.
Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
Sandra
S
Ribes
Jörn
J
Riegelmann
Sandra
S
Redlich
Beatriz
B
Maestro
Bas
B
de Waal
E W
EW
Meijer
Jesús M
JM
Sanz
Roland
R
Nau
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002794:Choline / Q000737:chemistry* / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000378:metabolism*
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D050091:Dendrimers; D002794:Choline