A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion.
Nerve damage is the hallmark of Mycobacterium leprae infection, which results from M. leprae invasion of the Schwann cell of the peripheral nervous system. We have recently shown that the laminin-2 isoform, specially the G domain of laminin alpha2 chain, on the Schwann cell-axon unit serves as an initial neural target for M. leprae. However, M. leprae surface molecules that mediate bacterial invasion of peripheral nerves are entirely unknown. By using human alpha2 laminins as a probe, a major 28-kDa protein in the M. leprae cell wall fraction that binds alpha2 laminins was identified. After N-terminal amino acid sequence analysis, PCR-based strategy was used to clone the gene that encodes this protein. Deduced amino acid sequence of this M. leprae laminin-binding protein predicts a 21-kDa molecule (ML-LBP21), which is smaller than the observed molecular size in SDS/PAGE. Immunofluorescence and immunoelectron microscopy on intact M. leprae with mAbs against recombinant (r) ML-LBP21 revealed that the protein is surface exposed. rML-LBP21 avidly bound to alpha2 laminins, the rG domain of the laminin-alpha2 chain, and the native peripheral nerve laminin-2. The role of ML-LBP21 in Schwann cell adhesion and invasion was investigated by using fluorescent polystyrene beads coated with rML-LBP21. Although beads coated with rML-LBP21 alone specifically adhered to and were ingested by primary Schwann cells, these functions were significantly enhanced when beads were preincubated with exogenous alpha2 laminins. Taken together, the present data suggest that ML-LBP21 may function as a critical surface adhesin that facilitates the entry of M. leprae into Schwann cells.
Shimoji
Y
Y
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10021, USA.
Ng
V
V
Matsumura
K
K
Fischetti
V A
VA
Rambukkana
A
A
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002473:Cell Wall / Q000737:chemistry; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D007918:Leprosy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000382:microbiology* / Q000473:pathology*; D012583:Schwann Cells / Q000382:microbiology* / Q000473:pathology*; D013499:Surface Properties
D018829:Adhesins, Bacterial; D007797:Laminin; C121018:ML-LBP21; C102645:laminin alpha 2