%0 Journal Article
%T Mycobacterium abscessus virulence traits unraveled by transcriptomic profiling in amoeba and macrophages
%A Alexandre Pawlik
%A Anouchka Bories
%A Fabienne Girard-Misguich
%A Hugo Varet
%A Jean-Louis Gaillard
%A Jean-Louis Herrmann
%A Jean-Yves Copp¨¦e
%A Mar¨ªa del Pilar Rodr¨ªguez-Ord¨®£¿ez
%A Odile Sismeiro
%A Rachel Legendre
%A Roland Brosch
%A Vincent Le Moigne
%A Violaine Dubois
%J -
%D 2019
%R 10.1371/journal.ppat.1008069
%X Free-living amoebae are thought to represent an environmental niche in which amoeba-resistant bacteria may evolve towards pathogenicity. To get more insights into factors playing a role for adaptation to intracellular life, we characterized the transcriptomic activities of the emerging pathogen Mycobacterium abscessus in amoeba and murine macrophages (M£¿) and compared them with the intra-amoebal transcriptome of the closely related, but less pathogenic Mycobacterium chelonae. Data on up-regulated genes in amoeba point to proteins that allow M. abscessus to resist environmental stress and induce defense mechanisms, as well as showing a switch from carbohydrate carbon sources to fatty acid metabolism. For eleven of the most upregulated genes in amoeba and/or M£¿, we generated individual gene knock-out M. abscessus mutant strains, from which ten were found to be attenuated in amoeba and/or M£¿ in subsequence virulence analyses. Moreover, transfer of two of these genes into the genome of M. chelonae increased the intra-M£¿ survival of the recombinant strain. One knock-out mutant that had the gene encoding Eis N-acetyl transferase protein (MAB_4532c) deleted, was particularly strongly attenuated in M£¿. Taken together, M. abscessus intra-amoeba and intra-M£¿ transcriptomes revealed the capacity of M. abscessus to adapt to an intracellular lifestyle, with amoeba largely contributing to the enhancement of M. abscessus intra-M£¿ survival
%K Transcriptome analysis
%K Mycobacterium tuberculosis
%K Amoebas
%K Intracellular pathogens
%K Mycobacteria
%K Autophagic cell death
%K Gene regulation
%K Gene expression
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008069