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Published on: January 17, 2014
Oligosaccharides interfere with the establishment and progression of experimental pneumococcal pneumonia
I Idänpään-Heikkilä1, P M Simon, D Zopf
1Rockefeller University, and Department of Radiology, New York Hospital-Cornell Medical Center, New York, USA.
Abstract:
Oligosaccharides that block the adherence of bacteria to epithelial cells in vitro--lacto-N-neotetraose (LNnT) and its alpha2-3- and alpha2-6-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 anti-adherence 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.
Insights
Lacto-N-neotetraose (LNnT) oligosaccharides prevent pneumococcal adherence and reduce infection severity. These compounds show promise as preventive and therapeutic agents for bacterial infectious diseases.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Bacterial adherence to epithelial cells is a key step in infection.
- Oligosaccharides can block bacterial adherence.
- Streptococcus pneumoniae causes pneumonia and nasopharyngeal colonization.
Purpose of the Study:
- To evaluate the efficacy of lacto-N-neotetraose (LNnT) and its derivatives in preventing and treating pneumococcal infections.
- To assess the potential of these oligosaccharides as therapeutic and preventive agents.
Main Methods:
- In vitro testing of oligosaccharide anti-adherence properties.
- Animal models (rabbits and infant rats) for pneumococcal pneumonia and nasopharyngeal colonization.
- Intratracheal and intranasal administration of oligosaccharides and bacteria.
Main Results:
- Oligosaccharides significantly reduced pneumococcal load in rabbit lungs and prevented bacteremia.
- Therapeutic administration of oligosaccharides ameliorated pneumonia and bacteremia.
- Intranasal administration prevented nasopharyngeal colonization in infant rats.
- LNnT induced changes in lung epithelial cells, inhibiting pneumococcal adherence.
Conclusions:
- LNnT and its derivatives demonstrate potent anti-adherence activity against Streptococcus pneumoniae.
- These oligosaccharides are effective in both preventing and treating pneumococcal infections in animal models.
- Oligosaccharides represent a promising class of agents for the development of novel preventive and therapeutic strategies against infectious diseases.
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