Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae

Cell. 2000 Oct 27;103(3):511-24. doi: 10.1016/s0092-8674(00)00142-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Bacterial*
  • Axons / drug effects
  • Axons / metabolism
  • Axons / microbiology
  • Axons / ultrastructure
  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Basement Membrane / microbiology
  • Basement Membrane / ultrastructure
  • Binding Sites
  • Cell Wall / chemistry
  • Cell Wall / metabolism*
  • Cell Wall / ultrastructure
  • Cells, Cultured
  • Coculture Techniques
  • Extracellular Matrix Proteins / metabolism
  • Glycolipids / chemistry
  • Glycolipids / metabolism*
  • Humans
  • Laminin / chemistry
  • Laminin / metabolism
  • Laminin / pharmacology
  • Microscopy, Electron
  • Microspheres
  • Mycobacterium leprae / cytology*
  • Mycobacterium leprae / pathogenicity
  • Mycobacterium leprae / physiology*
  • Mycobacterium leprae / radiation effects
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism
  • Nerve Fibers / microbiology
  • Nerve Fibers / ultrastructure
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Binding / drug effects
  • Protein Structure, Tertiary
  • Rats
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism
  • Schwann Cells / microbiology
  • Sciatic Nerve / cytology
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / microbiology*
  • Trisaccharides / metabolism
  • Trisaccharides / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antigens, Bacterial
  • Extracellular Matrix Proteins
  • Glycolipids
  • Laminin
  • Peptide Fragments
  • Trisaccharides
  • laminin alpha 2
  • phenolic glycolipid I, Mycobacterium leprae