The H37Rv and H37Ra strains of Mycobacterium tuberculosis were incubated with normal rabbit alveolar macrophages and examined by electron microscopy at 5 to 6 and 18 to 24 h of incubation. At the 18- to 24-h incubation interval, 60 to 100% of the endocytosed organisms of the H37Rv strain disrupted the phagosomal membranes and appeared free in the cytoplasm of the macrophages. In contrast, the H37Ra strain lacked this putative virulence characteristic, and greater than 99% of the organisms appeared within intact phagosomes. Heating the organisms of the H37Rv strain abrogated to a large extent, but not completely, their capacity to disrupt phagosomal membranes. In the course of the interaction of organisms of the virulent H37Rv strain with phagosomal membranes of normal rabbit alveolar macrophages, adherence of the phagosomal membrane to the surface of the organisms was a prominent feature that was followed by fragmentation and apparent disintegration of the membrane. This potential virulence characteristic could explain why there is essentially no resistance expressed in the lung during the early postinfectious period of primary infection to M. tuberculosis.
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