The human pathogenMycobacterium tuberculosisand the fish pathogenMycobacterium marinumtrigger the same core set of late innate immune response genes in zebrafish larvae

Abstract

AbstractZebrafish is a natural host of variousMycobacteriumspecies and a surrogate model organism for tuberculosis research.Mycobacterium marinumis evolutionarily one of the closest non-tuberculous species related toM. tuberculosisand shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos withM. tuberculosisand performed drug treatment of the infected larvae. In the present study we examined for how longM. tuberculosiscan be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Granuloma-like structures carrying fluorescently labeledM. tuberculosiscould be detected up to 9 days post infection. The continued presence of viableM. tuberculosisin the zebrafish larvae was further confirmed using the molecular bacterial load (MBL) assay. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the response of zebrafish larvae infected with the surrogate speciesM. marinum. We conclude thatM. tuberculosiscan be propagated in zebrafish larvae for at least one week after infection and provide further evidence thatM. marinumis a good surrogate model forM. tuberculosis.