A MYCOBACTERIUM-LEPRAE GENE ENCODING A FIBRONECTIN-BINDING PROTEIN ISUSED FOR EFFICIENT INVASION OF EPITHELIAL-CELLS AND SCHWANN-CELLS

Mycobacterium leprae, the causative agent of leprosy, is an obligate i ntracellular pathogen, M. leprae can infect a variety of cells in vivo , including epithelial cells, muscle cells, and Schwann cells, in addi tion to macrophages, The ligand-receptor interactions important in the attachment and ingestion of M. leprae by these nonmacrophage cells re mains unknown. Fibronectin (FN) significantly enhances both attachment and ingestion of M. leprae by epithelial and Schwann cell lines, We c loned an M, leprae FN binding protein (FN attachment protein [FAP]) di stinct 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 3 9-amino-acid signal peptide and was previously described as an antigen in leprosy patients. M. leprae FAP has homologies in M. vaccae, M. av ium, and M. tuberculosis, as determined by Southern blotting and direc t peptide analysis, Both anti-FAP antibodies and an Escherichia coli-e xpressed recombinant protein significantly blocked M. leprae attachmen t and internalization by T-24, an epithelial cell line, and JS1, a Sch wann cell line, These data suggest that FN can be a bridging opsonic l igand for attachment of mycobacteria to nonphagocytes and that FAP pla ys an important role in this process. This may be an important step in the initiation of M. leprae infection in vivo.