Immuno-pathogenesis of Mycobacterium abscessus in a new Xenopus tadpole model 3657

Abstract Description Non-tuberculosis mycobacteria M. abscessus (Mab) is an opportunistic pathogen increasingly causing diseases in humans, especially patients with immunocompromised conditions. We have developed the amphibian Xenopus as a comparative experimental organism to investigate pathogenesis and host resistance to Mab relevant for human health. We focused on a novel putative secondary metabolite pathway encoded in a gene cluster spanning MAB_0284c to 0305 that is related to Streptomyces pathways producing the secondary metabolites streptonigrin and nybomycin. We constructed an in-frame deletion of the MAB_0295 (phzC) gene and tested it in Xenopus tadpoles. We have shown that tadpoles, which have functional lungs and T cells, can serve as a reliable model for persistent Mab infection and pathogenesis. Our results suggests that tadpoles intraperitoneally infected with the ?phzC mutant exhibit reduced transcript levels of several pro-inflammatory cytokines (Il1b, tnfa, inos, ifng) in the liver and lungs as compared with WT Mab. Moreover, tail wound inoculation assay in tadpoles by intravital confocal microscopy reveals an impaired macrophage recruitment and decreased macrophage infection by ?phzC mutants compared to WT bacteria. These data underline the usefulness of Xenopus tadpoles as a novel model to identify genetic determinants of Mab immune-pathogenesis and suggests a role for this novel and uncharacterized pathway in Mab immune-pathogenesis. Funding Sources This study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (R24-AI059830; R21 5R21AI166114) Topic Categories Veterinary and Comparative Immunology (VET)