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

Alexandre Pawlik; Guillaume Garnier; Mickael Orgeur; Pin Tong; Amanda Lohan; Fabien Le Chevalier; Guillaume Sapriel; Anne-Laure Roux; Kevin Conlon; Nadine Honoré; Marie-Agnes Dillies; Laurence Ma; Christiane Bouchier; Jean-Yves Coppée; Jean-Louis Gaillard; Stephen Gordon; Brendan Loftus; Roland Brosch; Jean Louis Herrmann

doi:10.1111/mmi.12387

Journal articles

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology / Genomics [q-bio.GN]

Life Sciences [q-bio] / Microbiology and Parasitology / Bacteriology

Life Sciences [q-bio] / Human health and pathology / Emerging diseases

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https://hal-pasteur.archives-ouvertes.fr/pasteur-02618774
Contributor : Alexandre Pawlik <>
Submitted on : Monday, May 25, 2020 - 3:27:05 PM
Last modification on : Wednesday, June 16, 2021 - 7:06:02 PM

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

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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

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