Buruli ulcer research currently focuses on the role of mycolactone, the Mycobacterium ulcerans (Mul) exotoxin. However, interactions between Mul and macrophages during early infection are likely critical to disease outcome. We are investigating the utility of so-called ‘mycolactone-producing mycobacteria’ that are not known to cause disease in humans but induces Buruli ulcer-like infections in cold-blooded fish and frogs. We hypothesize that these could be useful as surrogates for Mul.  These strains, which require CL2 (not CL3) containment and are easier to genetically manipulate, could be as important for Buruli ulcer research as BCG is in TB. Our work provides the first evidence for the use of these nonpathogenic strains to interrogate host-pathogen interactions that could be important for pathogenesis. In the broader scope, we hope to use the fluorescently labelled strains to investigate marinum trafficking and subcellular localization in macrophages during early infection. Having successfully transformed these strains brings the promise of generating mutants to examine the role of mycolactone and other virulence genes inside macrophages.