Trafficking of Superinfecting Mycobacterium Organisms into Established Granulomas Occurs in Mammals and Is Independent of the Erp and ESX-1 Mycobacterial Virulence Loci

Although tuberculous granulomas, which are composed of infected macrophages and other immune cells, have long been considered impermeable structures, recent studies have shown that superinfecting Mycobacterium marinum traffic rapidly to established fish and frog granulomas by host-mediated and Mycobacterium-directed mechanisms. The present study shows that superinfecting Mycobacterium tuberculosis and Mycobacterium bovis bacille Calmette-Guerin similarly home to established granulomas in mice. Furthermore, 2 prominent mycobacterial virulence determinants, Erp and ESX-1, do not affect this cellular trafficking. These findings suggest that homing of infected macrophages to sites of infection is a general feature of the pathogenesis of tuberculosis and has important consequences for therapeutic strategies.