MYCOBACTERIUM-CONTAINING PHAGOSOMES ARE ACCESSIBLE TO EARLY ENDOSOMESAND REFLECT A TRANSITIONAL STATE IN NORMAL PHAGOSOME BIOGENESIS

The success of Mycobacterium as a pathogen hinges on its ability to mo dulate its intracellular environment. Mycobacterium avium reside in va cuoles with limited proteolytic activity, maintain cathepsin D in an i mmature form and remain accessible to internalized transferrin. Artifi cial acidification of isolated phagosomes facilitated processing of ca thepsin D, demonstrating that pH alone limits proteolysis in these vac uoles. Moreover, analysis of IgG-bead phagosomes at early time points during their formation indicates that these phagosomes also acquire LA MP 1 and cathepsin D prior to the accumulation of proton-ATPases, and are transiently accessible to sorting endosomes. This suggests that th e anomolous distribution of endosomal proteins in M.avium-containing v acuoles results from their arrested differentiation in an early transi tional stage through which all phagosomes pass.