Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry

The ability to gain entry and resist the antimicrobial intracellular enviro nment of mammalian cells is an essential virulence property of Mycobacteriu m tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of po lystyrene latex microspheres coated with the protein. N-terminus deletion c onstructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained h ydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained fo ur homologues of mce (mce1, mce2, mce3, mce4) and that they were all locate d within operons composed of genes arranged similarly at different location s in the chromosome. Recombinant Mce2, which had the highest level of ident ity (67%) to Mce1, was unable to promote the association of microspheres wi th HeLa cells. Although the exact function of Mce1 is still unknown, it app ears to serve as an effector molecule expressed on the surface of M. tuberc ulosis that is capable of eliciting plasma membrane perturbations in non-ph agocytic mammalian cells.