An electron microscopy study of intra-cellular mycobacteria in experimental mouse tuberculosis

Ultra-thin sections for electron microscopy (EM) were prepared from granulomatous lungs which developed in mice in response to experimental infection by a highly virulent strain of M. bovis. A subsidiary study was made of the EM appearance of mycobacteria separated from the lung tissue homogenate by differential centrifugation and trypsin-digestion. Examination of many micrographs showed that the phagosomal membrane may, at least partly, be in close contact with the cell wall of ingested mycobacteria. Such areas of contact often produce an electron-dense granularity or a row of evenly-spaced minute granules, accompanying the damage to the inner structure of the bacterial cell. A variety of disintegrating bacterial figures were observed, characterized by inward detachment of the plasma membrane, shrinkage and digestion of the cytoplasm, and occasional rupture of the cell wall. Various forms of lamellated and osmophilic inclusion bodies were present in macrophages, but their relation to ingested mycobacteria was uncertain.