Association between the infectivity of Mycobacterium tuberculosis strains and their efficiency for extrarespiratory infection.

Extrarespiratory tuberculosis is determined mainly by impaired immunity of the host. The additional role played by bacterial factors in determining whether an infection by Mycobacterium tuberculosis disseminates to extrarespiratory sites has not been analyzed in depth. In the present study, we selected patients who were dually infected with 2 M. tuberculosis strains but in whom only one of the strains infected extrarespiratory sites, whereas the other strain remained at the respiratory site. We compared the infectivity of respiratory and extrarespiratory strains in a newly designed ex vivo competitive macrophage coinfection assay and in the murine aerosol-infection model. The extrarespiratory strains infected macrophages more efficiently than did the respiratory strains, and a representative extrarespiratory strain also showed higher infectivity in vivo. Our data indicate that, in addition to host immune status, a bacterial factor--the infectivity of a M. tuberculosis strain--should be considered in determining the likelihood of extrarespiratory dissemination.