A Mycobacterium leprae gene encoding a fibronectin binding protein is used for efficient invasion of epithelial cells and Schwann cells.
Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen. M. leprae can infect a variety of cells in vivo, including epithelial cells, muscle cells, and Schwann cells, in addition to macrophages. The ligand-receptor interactions important in the attachment and ingestion of M. leprae by these nonmacrophage cells remains unknown. Fibronectin (FN) significantly enhances both attachment and ingestion of M. leprae by epithelial and Schwann cell lines. We cloned an M. leprae FN binding protein (FN attachment protein [FAP]) distinct from the 85ABC complex which has been shown previously to bind FN. The FAP open reading frame predicts a protein of 29.5 kDa with a 39-amino-acid signal peptide and was previously described as an antigen in leprosy patients. M. leprae FAP has homologies in M. vaccae, M. avium, and M. tuberculosis, as determined by Southern blotting and direct peptide analysis. Both anti-FAP antibodies and an Escherichia coli-expressed recombinant protein significantly blocked M. leprae attachment and internalization by T-24, an epithelial cell line, and JS1, a Schwann cell line. These data suggest that FN can be a bridging opsonic ligand for attachment of mycobacteria to nonphagocytes and that FAP plays an important role in this process. This may be an important step in the initiation of M. leprae infection in vivo.
Schorey
J S
JS
Department of Internal Medicine, Washington University School of Medicine, St. Louis Missouri 63110, USA.
Li
Q
Q
McCourt
D W
DW
Bong-Mastek
M
M
Clark-Curtiss
J E
JE
Ratliff
T L
TL
Brown
E J
EJ
D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004848:Epithelium / Q000382:microbiology; D005353:Fibronectins / Q000378:metabolism*; D015870:Gene Expression; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000235:genetics / Q000472:pathogenicity*; D015345:Oligonucleotide Probes / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D012583:Schwann Cells / Q000382:microbiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; C094291:fibronectin-attachment protein, Mycobacterium leprae