Primary tuberculous mycobacterial granulomas provide a niche for superinfecting Mycobacterium abscessus

Prior and concurrent Mycobacterium 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. We find other opportunistic pathogens Mycobacterium smegmatis, Aspergillus fumigatus, and Candida auris are also able to colonize and preferentially grow inside primary M. marinum granulomas. Rapid growth of M. abscessus is driven by feeding on caseum produced by the primary M. marinum ESX-1 virulence program in a nutritionally separate niche from M. marinum. In this work we show tuberculous granulomas may provide a long-lasting niche for the growth of the opportunistic pathogen M. abscessus.