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Identification and characterization of the genetic changes responsible for the characteristic smooth-to-rough morphotype alterations of clinically persistent Mycobacterium abscessus

Alexandre Pawlik 1, 2, 3 Guillaume Garnier 1, 2 Mickael Orgeur 3 Pin Tong 4 Amanda Lohan 4 Fabien Le Chevalier 3 Guillaume Sapriel 1, 2 Anne-Laure Roux 1, 2 Kevin Conlon 4 Nadine Honoré 5 Marie-Agnes Dillies 6 Laurence Ma 7 Christiane Bouchier 8 Jean-Yves Coppée 6 Jean-Louis Gaillard 1, 2 Stephen Gordon 4 Brendan Loftus 4 Roland Brosch 3, * Jean Louis Herrmann 1, 2, *
* Corresponding author
1 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
2 Service de Microbiologie [Garches]
3 Pathogénomique mycobactérienne intégrée
4 Conway Institute
5 Génétique Moléculaire Bactérienne
6 PF2 - Transcriptome et Epigénome
7 C2RT - Pôle Biomics
8 Génomique (Plate-Forme) - Genomics Platform
Abstract : Mycobacterium abscessus is an emerging pathogen that is increasingly recognized as a relevant cause of human lung infection in cystic fibrosis patients. This highly antibiotic-resistant mycobacterium is an exception within the rapidly growing mycobacteria, which are mainly saprophytic and non-pathogenic organisms. M. abscessus manifests as either a smooth (S) or a rough (R) colony morphotype, which is of clinical importance as R morphotypes are associated with more severe and persistent infections. To better understand the molecular mechanisms behind the S/R alterations, we analysed S and R variants of three isogenic M. abscessus S/R pairs using an unbiased approach involving genome and transcriptome analyses, transcriptional fusions and integrating constructs. This revealed different small insertions, deletions (indels) or single nucleotide polymorphisms within the non-ribosomal peptide synthase gene cluster mps1-mps2-gap or mmpl4b in the three R variants, consistent with the transcriptional differences identified within this genomic locus that is implicated in the synthesis and transport of Glyco-Peptido-Lipids (GPL). In contrast to previous reports, the identification of clearly defined genetic lesions responsible for the loss of GPL-production or transport makes a frequent switching back-and-forth between smooth and rough morphologies in M. abscessus highly unlikely, which is important for our understanding of persistent M. abscessus infections.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02618774
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Submitted on : Monday, May 25, 2020 - 3:27:05 PM
Last modification on : Wednesday, December 1, 2021 - 4:40:02 PM

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Alexandre Pawlik, Guillaume Garnier, Mickael Orgeur, Pin Tong, Amanda Lohan, et al.. Identification and characterization of the genetic changes responsible for the characteristic smooth-to-rough morphotype alterations of clinically persistent Mycobacterium abscessus. Molecular Microbiology, Wiley, 2013, 90 (3), pp.612-629. ⟨10.1111/mmi.12387⟩. ⟨pasteur-02618774⟩

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