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

English version

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): e1008069. doi:10.1371/journal.ppat.1008069
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/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:

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

Zdroje

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