Primary tuberculous mycobacterial granulomas provide a niche for superinfecting Mycobacterium abscessus

Prior and concurrent tuberculosis infection are among the most important susceptibility factors for nontuberculous mycobacterial infection in Asia. Here we model this process in zebrafish with a primaryMycobacterium marinuminfection followed by a secondaryM. abscessusinfection. We demonstrate preferential growth of secondaryM. abscessusinfection inside primaryM. marinumgranulomas. Granuloma-resident secondaryM. abscessusis protected from macrophage-mediated immune control and antibiotic therapy. Successful colonization is driven by expansion ofM. abscessusfeeding on caseum produced by the primaryM. marinumESX-1 virulence program in a nutritionally separate niche fromM. marinum. Our data suggest tuberculous granulomas may provide a long-lasting niche for the growth of the opportunistic pathogenMycobacterium abscessus.