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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Proteoglycans in host-pathogen interactions: molecular mechanisms and therapeutic implications
Allison H Bartlett1, Pyong Woo Park
1Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Many microbial pathogens subvert proteoglycans for their adhesion to host tissues, invasion of host cells, infection of neighbouring cells, dissemination into the systemic circulation, and evasion of host defence mechanisms. Where studied, specific virulence factors mediate these proteoglycan-pathogen interactions, which are thus thought to affect the onset, progression and outcome of infection. Proteoglycans are composites of glycosaminoglycan (GAG) chains attached covalently to specific core proteins. Proteoglycans are expressed ubiquitously on the cell surface, in intracellular compartments, and in the extracellular matrix. GAGs mediate the majority of ligand-binding activities of proteoglycans, and many microbial pathogens elaborate cell-surface and secreted factors that interact with GAGs. Some pathogens also modulate the expression and function of proteoglycans through known virulence factors. Several GAG-binding pathogens can no longer attach to and invade host cells whose GAG expression has been reduced by mutagenesis or enzymatic treatment. Furthermore, GAG antagonists have been shown to inhibit microbial attachment and host cell entry in vitro and reduce virulence in vivo. Together, these observations underscore the biological significance of proteoglycan-pathogen interactions in infectious diseases.
Insights
Microbial pathogens use proteoglycans, which are cell surface molecules, to infect host cells. Disrupting these interactions with glycosaminoglycan (GAG) antagonists can inhibit pathogen invasion and reduce disease.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Proteoglycans, composed of glycosaminoglycan (GAG) chains and core proteins, are crucial for cell surface and extracellular matrix functions.
- Many microbial pathogens exploit proteoglycans for critical steps in infection, including adhesion, invasion, and dissemination.
- Pathogen interactions with proteoglycans significantly influence the onset, progression, and outcome of infectious diseases.
Purpose of the Study:
- To investigate the role of proteoglycan-pathogen interactions in microbial pathogenesis.
- To understand how specific virulence factors mediate these interactions.
- To explore the therapeutic potential of targeting proteoglycan-pathogen interactions.
Main Methods:
- Review of existing literature on microbial pathogenesis and proteoglycan function.
- Analysis of studies involving GAG-binding pathogens and their interactions with host proteoglycans.
- Examination of experimental evidence, including mutagenesis, enzymatic treatments, and the use of GAG antagonists.
Main Results:
- Microbial pathogens utilize proteoglycans for adhesion, invasion, cell-to-cell spread, systemic dissemination, and immune evasion.
- Specific virulence factors mediate pathogen interactions with proteoglycans, impacting infection dynamics.
- Reduced GAG expression significantly impairs pathogen attachment and invasion.
- GAG antagonists effectively inhibit microbial attachment and host cell entry in vitro and reduce virulence in vivo.
Conclusions:
- Proteoglycan-pathogen interactions are biologically significant in infectious diseases.
- Targeting these interactions, particularly via GAG antagonists, presents a promising strategy for therapeutic intervention against microbial infections.
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