Human lactoferrin proteolytic activity: analysis of the cleaved region in the IgA protease of Haemophilus influenzae.

Human lactoferrin proteolytically cleaves and inactivates two colonization factors of non-typable Haemophilus influenzae, the IgA protease precursor protein (Iga), and Hap, the non-pilus adhesin by which microoganisms adhere to host epithelial cells and form microcolonies. Iga and Hap are homologous proteins that are members of the autotransporter family of secreted proteins expressed by gram-negative bacteria. Studies of Iga cleaved by lactoferrin, reported here, show that proteolysis occurred within the helper region of Iga (Iga(beta)) domain which anchors the autotransporter within the Haemophilus outer membrane. The amino-terminus of the extracted Iga protein was not modified. The location of the proteolytic active site in human lactoferrin is under study. Lactoferrin proteolysis may attenuate pathogenicity of H. influenzae, an important cause of otitis media.