Oligosaccharides Interfere with the Establishment and Progression of Experimental Pneumococcal Pneumonia

Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro—lacto-N-neotetraose (LNnT) and its α2-3- and α2-6-sialylated derivatives—were tested for their abilities to attenuate the course of pneumococcal pneumonia and to prevent colonization of the nasopharynx in animal model...

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Bibliographic Details
Published in:The Journal of infectious diseases 1997-09, Vol.176 (3), p.704-712
Main Authors: Idänpään-Heikkilä, Ilona, Simon, Paul M., Zopf, David, Vullo, Thomas, Cahill, Patrick, Sokol, Karen
Format: Article
Language:English
Subjects:
Animals
Bacteremia
Bacteremia - drug therapy
Bacteremia - microbiology
Bacteria
Bacterial Adhesion - drug effects
Bacteriology
Biogenesis of cell structures, supramolecular organization
Biological and medical sciences
Blood
Carbohydrate Sequence
Carbohydrates
Cell Line
Fundamental and applied biological sciences. Psychology
Lung - drug effects
Lung - microbiology
Lungs
Magnetic resonance imaging
Major Articles
Microbiology
Molecular Sequence Data
Nasopharynx - microbiology
Oligosaccharides
Oligosaccharides - pharmacology
Pneumococcal pneumonia
Pneumonia, Pneumococcal - drug therapy
Pneumonia, Pneumococcal - prevention & control
Rabbits
Rats
Receptors
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
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Summary:Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro—lacto-N-neotetraose (LNnT) and its α2-3- and α2-6-sialylated derivatives—were tested for their abilities to attenuate the course of pneumococcal pneumonia and to prevent colonization of the nasopharynx in animal models. Intratracheal administration of these agents concurrently with bacteria dramatically decreased pneumococcal load in the lungs of rabbits and conferred protection from bacteremia. The oligosaccharides ameliorated pneumonia and bacteremia when given therapeutically 24 h after infection was established. When administered intranasally, neoglycoconjugates of the active oligosaccharides prevented colonization of the nasopharynx of infant rats. In addition to in vitro antiadherence properties, LNnT acted directly on cultured lung epithelial cell lines to induce changes such that pneumococcal adherence was prevented for prolonged periods. These activities encourage continued development of oligosaccharides as a class of potentially preventive and therapeutic agents for infectious diseases.
ISSN:0022-1899
1537-6613
DOI:10.1086/514094