Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae.
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.
Ng
V
V
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York 10021, USA.
Zanazzi
G
G
Timpl
R
R
Talts
J F
JF
Salzer
J L
JL
Brennan
P J
PJ
Rambukkana
A
A
D000818:Animals; D000942:Antigens, Bacterial; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D001665:Binding Sites; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D018920:Coculture Techniques; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006017:Glycolipids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008854:Microscopy, Electron; D008863:Microspheres; D009166:Mycobacterium leprae / Q000166:cytology* / Q000472:pathogenicity / Q000502:physiology* / Q000528:radiation effects; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D014312:Trisaccharides / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D016326:Extracellular Matrix Proteins; D006017:Glycolipids; D007797:Laminin; D010446:Peptide Fragments; D014312:Trisaccharides; C102645:laminin alpha 2; C045169:phenolic glycolipid I, Mycobacterium leprae