Primary tuberculous mycobacterial granulomas provide a niche for superinfecting Mycobacterium abscessus

Abstract

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 primary Mycobacterium marinum infection followed by a secondary M. abscessus infection. We demonstrate preferential growth of secondary M. abscessus infection inside primary M. marinum granulomas. Granuloma-resident secondary M. abscessus is protected from macrophage-mediated immune control and antibiotic therapy. Successful colonization is driven by expansion of M. abscessus feeding on caseum produced by the primary M. marinum ESX-1 virulence program in a nutritionally separate niche from M. marinum. Our data suggest tuberculous granulomas may provide a long-lasting niche for the growth of the opportunistic pathogen Mycobacterium abscessus.