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Leprosy is a chronic infection where the skin and peripheral nervous system is invaded by  Mycobacterium leprae . The infection mechanism remains unknown in part because culture methods have not been established yet for  M .  leprae . Mce1A protein (442 aa) is coded by  mce1A  (1326 bp) of  M .  leprae . The Mce1A homolog in  Mycobacterium tuberculosis  is known to be associated with  M .  tuberculosis  epithelial cell entry, and survival and multiplication within macrophages. Studies using recombinant proteins have indicated that Mce1A of  M .  leprae  is also associated with epithelial cell entry. This study is aimed at identifying particular sequences within Mce1A associated with  M .  leprae  epithelial cell entry. Recombinant proteins having N-terminus and C-terminus truncations of the Mce1A region of  M .  leprae  were created in  Escherichia coli . Entry activity of latex beads, coated with these truncated proteins (r-lep37 kDa and r-lep27 kDa), into HeLa cells was observed by electron microscopy. The entry activity was preserved even when 315 bp (105 aa) and 922 bp (308 aa) was truncated from the N-terminus and C-terminus, respectively. This 316–921 bp region was divided into three sub-regions: 316–531 bp (InvX), 532–753 bp (InvY), and 754–921 bp (InvZ). Each sub-region was cloned into an AIDA vector and expressed on the surface of  E .  coli . Entry of these  E .  coli  into monolayer-cultured HeLa and RPMI2650 cells was observed by electron microscopy. Only  E .  coli  harboring the InvX sub-region exhibited cell entry. InvX was further divided into 4 domains, InvXa—InvXd, containing sequences 1–24 aa, 25–46 aa, 47–57 aa, and 58–72 aa, respectively. Recombinant  E .  coli , expressing each of InvXa—InvXd on the surface, were treated with antibodies against these domains, then added to monolayer cultured RPMI cells. The effectiveness of these antibodies in preventing cell entry was studied by colony counting. Entry activity was suppressed by antibodies against InvXa, InvXb, and InvXd. This suggests that these three InvX domains of Mce1A are important for  M .  leprae  invasion into nasal epithelial cells.

The unique tropism of Mycobacterium leprae to the nasal epithelial cells can be explained by the mammalian cell entry protein 1A