Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages

Despite the antimicrobial mechanisms of vertebrate phagocytes, mycobacteria can survive within the phagosomes of these cells. These organisms use vari ous strategies to evade destruction, including inhibition of acidification of the phagosome and inhibition of phagosome-lysosome fusion. In contrast t o mycobacteria, Coxiella burnetii, the etiologic agent of Q fever, inhabits a spacious acidified intracellular vacuole which is prone to fusion with o ther vacuoles of the host tell, including phagosomes containing mycobacteri a. The Coxiella-infected cell thus provides a unique model for investigatin g the survival of mycobacteria in an acidified phagosome-like compartment. In the present study, murine bane marrow-derived macrophages were infected with either Mycobacterium avium or Mycobacterium tuberculosis and then coin fected with C. burnetii. We observed that the majority of phagocytosed myco bacteria colocalized to the C. burnetii-containing vacuole, which maintaine d its acidic properties. In coinfected macrophages, the growth of M. avium was not impaired following fusion with the acidified vacuole. In contrast, the growth rate of M. tuberculosis was reduced in acidified vacuoles. These results suggest that although both species of mycobacteria inhibit phagoso me-lysosome fusion, they may be differentially susceptible to the toxic eff ects of the acidic environment in the mature phagolysosome.