title: Identification and characterization of the genetic changes responsible for the characteristic smooth-to-rough morphotype alterations of clinically persistent Mycobacterium abscessus.
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.
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France; EA 3647, University Versailles St Quentin in Yvelines, Garches, France; Microbiology Laboratory, Assistance Publique - Hôpitaux de Paris, Raymond Poincaré Hospital, Garches, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pawlik
authors.forename: Guillaume
authors.initials: G
authors.lastname: Garnier
authors.forename: Mickael
authors.initials: M
authors.lastname: Orgeur
authors.forename: Pin
authors.initials: P
authors.lastname: Tong
authors.forename: Amanda
authors.initials: A
authors.lastname: Lohan
authors.forename: Fabien
authors.initials: F
authors.lastname: Le Chevalier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sapriel
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Roux
authors.forename: Kevin
authors.initials: K
authors.lastname: Conlon
authors.forename: Nadine
authors.initials: N
authors.lastname: Honoré
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dillies
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gaillard
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Gordon
authors.forename: Brendan
authors.initials: B
authors.lastname: Loftus
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Herrmann
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D054643:INDEL Mutation; D008055:Lipids / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009161:Mycobacterium / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D010453:Peptide Synthases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D001426:Bacterial Proteins; D008055:Lipids; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase