Cytotoxicity for lung epithelial cells is a virulence-associated phenotype of Mycobacterium tuberculosis

Dissemination of viable tubercle bacilli from the lung is a critical event in the establishment of Mycobacterium tuberculosis infection. We examined the possibility that M. tuberculosis bacteria could infect and damage lung epithelial cells to determine whether direct penetration of the alveolar epithelium is a plausible route of M. tuberculosis infection. While both virulent H37Rv tubercle bacilli and the attenuated Mycobacterium bovis BCG vaccine strain were able to enter A549 human lung epithelial cells in culture, only the virulent tubercle bacilli were cytotoxic for both polarized and nonpolarized epithelial monolayers and macrophages. In addition, bacterial entry into epithelial cells, but not macrophages, was increased by intracellular passage through macrophages, suggesting enhancement of a bacterially mediated cell entry mechanism in bacteria grown within macrophages. These findings suggest that M. tuberculosis bacteria might have the ability to gain access to the host lymphatics and circulatory system by directly penetrating the alveolar epithelial lining of an infected lung.