Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry.
The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic 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 four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.
Chitale
S
S
Department of Medicine, Weill Medical College of Cornell University New York, NY, USA.
Ehrt
S
S
Kawamura
I
I
Fujimura
T
T
Shimono
N
N
Anand
N
N
Lu
S
S
Cohen-Gould
L
L
Riley
L W
LW
D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002462:Cell Membrane / Q000382:microbiology / Q000648:ultrastructure; D004926:Escherichia coli; D005798:Genes, Bacterial; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D016253:Microscopy, Immunoelectron; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D016366:Open Reading Frames; D009876:Operon; D011994:Recombinant Proteins / Q000378:metabolism
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins