|Title||Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae.|
|Publication Type||Journal Article|
|Year of Publication||2000|
|Authors||Ng V, Zanazzi G, Timpl R, Talts JF, Salzer JL, Brennan PJ, Rambukkana A|
|Date Published||2000 Oct 27|
|Keywords||Animals, Antigens, Bacterial, Axons, Basement Membrane, Binding Sites, Cell Wall, Cells, Cultured, Coculture Techniques, Extracellular Matrix Proteins, Glycolipids, Humans, Laminin, Microscopy, Electron, Microspheres, Mycobacterium leprae, Nerve Fibers, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Rats, Schwann Cells, Sciatic Nerve, Trisaccharides, Tumor Cells, Cultured|
The cell wall of pathogenic mycobacteria is abundant with complex glycolipids whose roles in disease pathogenesis are mostly unknown. Here, we provide evidence for the involvement of the specific trisaccharide unit of the phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae in determining the bacterial predilection to the peripheral nerve. PGL-1 binds specifically to the native laminin-2 in the basal lamina of Schwann cell-axon units. This binding is mediated by the alpha(2LG1, alpha2LG4, and alpha2LG5 modules present in the naturally cleaved fragments of the peripheral nerve laminin alpha2 chain, and is inhibited by the synthetic terminal trisaccharide of PGL-1. PGL-1 is involved in the M. leprae invasion of Schwann cells through the basal lamina in a laminin-2-dependent pathway. The results indicate a novel role of a bacterial glycolipid in determining the nerve predilection of a human pathogen.