Mycobacterium smegmatis laminin-binding glycoprotein shares epitopes with Mycobacterium tuberculosis heparin-binding haemagglutinin

Mycobacterium tuberculosis, the causative agent of tuberculosis, produces a heparin-binding haemagglutinin adhesin (HBHA), which is involved in its ep ithelial adherence. To ascertain whether HBHA is also present in fast-growi ng mycobacteria, Mycobacterium smegmatis was studied using anti-HBHA monocl onal antibodies (mAbs). A cross-reactive protein was detected by immunoblot ting of M. smegmatis whole-cell lysates. However, the M. tuberculosis HBHA- encoding gene failed to hybridize with M. smegmatis chromosomal DNA in Sout hern blot analyses. The M. smegmatis protein recognized by the anti-HBHA mA bs was purified by heparin-Sepharose chromatography, and its amino-terminal sequence was found to be identical to that of the previously described his tone-like protein, indicating that M. smegmatis does not produce HBHA. Bioc hemical analysis of the M. smegmatis histone-like protein shows that it is glycosylated like HBHA. Immunoelectron microscopy demonstrated that the M. smegmatis protein is present on the mycobacterial surface, a cellular local ization inconsistent with a histone-like function, but compatible with an a dhesin activity. In vitro protein interaction assays showed that this glyco protein binds to laminin, a major component of basement membranes. Therefor e, the protein was called M. smegmatis laminin-binding protein (MS-LBP). MS -LBP does not appear to be involved in adherence in the absence of laminin but is responsible for the laminin-mediated mycobacterial adherence to huma n pneumocytes and macrophages. Homologous laminin-binding adhesins are also produced by virulent mycobacteria such as M. tuberculosis and Mycobacteriu m leprae, suggesting that this adherence mechanism may contribute to the pa thogenesis of mycobacterial diseases.