Mycobacterium abscessus virulence traits unraveled by transcriptomic profiling in amoeba and macrophages


Autoři: Violaine Dubois aff001;  Alexandre Pawlik aff002;  Anouchka Bories aff001;  Vincent Le Moigne aff001;  Odile Sismeiro aff003;  Rachel Legendre aff003;  Hugo Varet aff003;  María del Pilar Rodríguez-Ordóñez aff005;  Jean-Louis Gaillard aff001;  Jean-Yves Coppée aff003;  Roland Brosch aff002;  Jean-Louis Herrmann aff001;  Fabienne Girard-Misguich aff001
Působiště autorů: Université Paris-Saclay, UVSQ, Inserm, Infection et inflammation, Montigny-Le-Bretonneux, France aff001;  Institut Pasteur, Unité de Pathogénomique Mycobactérienne intégrée, UMR3525 CNRS, Paris, France aff002;  Institut Pasteur—Bioinformatics and Biostatistics Hub—C3BI, USR 3756 IP CNRS, Paris, France aff003;  Institut Pasteur—Transcriptome and Epigenome Platform—Biomics Pole—CITECH, Paris, France aff004;  Laboratoire d'Écologie, Systématique et Évolution, Université Paris-Saclay, Orsay, France aff005;  AP-HP. GHU Paris Saclay, Hôpital Ambroise Paré, Boulogne Billancourt, France aff006;  AP-HP. GHU Paris Saclay, Hôpital Raymond Poincaré, Garches, France aff007
Vyšlo v časopise: Mycobacterium abscessus virulence traits unraveled by transcriptomic profiling in amoeba and macrophages. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008069
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008069

Souhrn

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 (Mϕ) 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 Mϕ, we generated individual gene knock-out M. abscessus mutant strains, from which ten were found to be attenuated in amoeba and/or Mϕ in subsequence virulence analyses. Moreover, transfer of two of these genes into the genome of M. chelonae increased the intra-Mϕ 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 Mϕ. Taken together, M. abscessus intra-amoeba and intra-Mϕ transcriptomes revealed the capacity of M. abscessus to adapt to an intracellular lifestyle, with amoeba largely contributing to the enhancement of M. abscessus intra-Mϕ survival.

Klíčová slova:

Autophagic cell death – Gene expression – Gene regulation – Intracellular pathogens – Mycobacteria – Mycobacterium tuberculosis – Transcriptome analysis – Amoebas


Zdroje

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