Identification of a 68 kd surface antigen of Mycobacterium avium that binds to human macrophages

Infection caused by Mycobacterium avium is the major cause of bacteremia in patients with AIDS. A critical event in the initiation of a variety of bacterial infections is the adherence of bacteria to host cell surfaces, which is often brought about by the interaction of specific molecules on the bacterial surface with host cell surface receptors. In the present study, a sonicate of M. avium was used to isolate monocyte-binding proteins by affinity chromatography with CNBr-Sepharose-4B coupled to extracts of monocytes. A 68 kd protein present on the surface of M. avium was identified as one of nine monocyte-binding proteins. This protein was isolated and further characterized. The N-terminal amino acid sequence (22 residues) of the protein was determined and was found to exhibit strong homology with the 65 kd heat shock proteins of M. tuberculosis, M. leprae, and M. bovis. However, a previously characterized monoclonal antibody directed against a 66 kd antigen of M. avium was found to cross-react with the 68 kd protein from M. avium but not with the 65 kd proteins from M. leprae and M. bovis, suggesting that the 68 kd antigen may differ from the 65 kd proteins of M. leprae and M. bovis with respect to certain epitopes. In an in vitro inhibition assay, the 68 kd protein was found to compete with the attachment of intact fluorescein isothiocyanate-labeled M. avium to monocyte-derived macrophages, inhibiting this attachment in a dose-dependent manner up to 42%. The 65 kd proteins of M. leprae and M. bovis, on the other hand, did not appear to inhibit this attachment substantially (13.9% and 14.6%, respectively). These results suggest that the 68 kd protein of M. avium may be involved in binding to receptors on macrophages and help in the attachment of the organism to its host cell.