title: Genome-wide mosaicism within Mycobacterium abscessus: evolutionary and epidemiological implications.
abstract: BACKGROUND
  In mycobacteria, conjugation differs from the canonical Hfr model, but is still poorly understood. Here, we quantified this evolutionary processe in a natural mycobacterial population, taking advantage of a large clinical strain collection of the emerging pathogen Mycobacterium abscessus (MAB).
  
  
  RESULTS
  Multilocus sequence typing confirmed the existence of three M. abscessus subspecies, and unravelled extensive allelic exchange between them. Furthermore, an asymmetrical gene flow occurring between these main lineages was detected, resulting in highly admixed strains. Intriguingly, these mosaic strains were significantly associated with cystic fibrosis patients with lung infections or chronic colonization. Genome sequencing of those hybrid strains confirmed that half of their genomic content was remodelled in large genomic blocks, leading to original tri-modal 'patchwork' architecture. One of these hybrid strains acquired a locus conferring inducible macrolide resistance, and a large genomic insertion from a slowly growing pathogenic mycobacteria, suggesting an adaptive gene transfer. This atypical genomic architecture of the highly recombinogenic strains is consistent with the distributive conjugal transfer (DCT) observed in M. smegmatis. Intriguingly, no known DCT function was found in M. abscessus chromosome, however, a p-RAW-like genetic element was detected in one of the highly admixed strains.
  
  
  CONCLUSIONS
  Taken together, our results strongly suggest that MAB evolution is sporadically punctuated by dramatic genome wide remodelling events. These findings might have far reaching epidemiological consequences for emerging mycobacterial pathogens survey in the context of increasing numbers of rapidly growing mycobacteria and M. tuberculosis co-infections.
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. guillaume.sapriel@uvsq.fr.|Laboratoire des Sciences du Climat et de l'Environnement, LSCE, UMR8212, Université de Versailles St. Quentin - CEA - CNRS, Saint-Aubin, France. guillaume.sapriel@uvsq.fr.|Atelier de Bioinformatique, ISYEB, UMR 7205, Paris, France. guillaume.sapriel@uvsq.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sapriel
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. konjek.julie@gmail.com.|AP-HP, Hôpital Ambroise Paré, Service de Microbiologie et Hygiène, Boulogne-Billancourt, France. konjek.julie@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Konjek
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France. orgeur@molgen.mpg.de.
authors.forename: Mickael
authors.initials: M
authors.lastname: Orgeur
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. laurent.bouri@ens.uvsq.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bouri
authors.affiliation: Institut of Biology of the Ecole Normale Supérieure, 46 rue d'Ulm, 75230, Paris, Cedex 05, France. frezal@biologie.ens.fr.
authors.forename: Lise
authors.initials: L
authors.lastname: Frézal
authors.affiliation: PF1-Plate-Forme Génomique, Institut Pasteur, Paris, France. anne-laure.roux@rpc.aphp.fr.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Roux
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. emilie.dumas26@gmail.com.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dumas
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, Paris, France. roland.brosch@pasteur.fr.
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.affiliation: PF1-Plate-Forme Génomique, Institut Pasteur, Paris, France. bouchier@pasteur.fr.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.affiliation: Institut Pasteur, Genotyping of Pathogens and Public Health, Paris, France. sbrisse@pasteur.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.affiliation: Institut Pasteur, Genotyping of Pathogens and Public Health, Paris, France. mathias.vandenbogaert@pasteur.fr.
authors.forename: Mathias
authors.initials: M
authors.lastname: Vandenbogaert
authors.affiliation: Institut Pasteur, Genotyping of Pathogens and Public Health, Paris, France. jean-michel.thiberge@pasteur.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Thiberge
authors.affiliation: Institut Pasteur, Genotyping of Pathogens and Public Health, Paris, France. valerie.caro@pasteur.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Caro
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. yunngeow@yahoo.com.
authors.forename: Yun Fong
authors.initials: YF
authors.lastname: Ngeow
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. tjl2309@hotmail.com.
authors.forename: Joon Liang
authors.initials: JL
authors.lastname: Tan
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. jean-louis.herrmann@rpc.aphp.fr.|AP-HP, Hôpital Raymond Poincaré, Service de Microbiologie et Hygiène, Garches, France. jean-louis.herrmann@rpc.aphp.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Herrmann
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. jean-louis.gaillard@apr.aphp.fr.|AP-HP, Hôpital Ambroise Paré, Service de Microbiologie et Hygiène, Boulogne-Billancourt, France. jean-louis.gaillard@apr.aphp.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gaillard
authors.affiliation: EA3647-EPIM, UFR des Sciences de La Santé, Université de Versailles St. Quentin, Montigny le Bretonneux, France. beate.heym@apr.aphp.fr.|AP-HP, Hôpital Ambroise Paré, Service de Microbiologie et Hygiène, Boulogne-Billancourt, France. beate.heym@apr.aphp.fr.
authors.forename: Beate
authors.initials: B
authors.lastname: Heym
authors.affiliation: Laboratoire de Biologie intégrative des populations, Evolution moléculaire, Ecole Pratique des Hautes Etudes, Paris, France. wirth@mnhn.fr.|Institut de Systématique, Evolution, Biodiversité, ISYEB, UMR 7205, CNRS, MNHN, UPMC, EPHE, Muséum national d'Histoire naturelle, Sorbonne Universités, 16 rue Buffon, F-75231, Paris, Cedex 05, France. wirth@mnhn.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wirth
mesh_terms: D015373:Bacterial Typing Techniques; D055028:Comparative Genomic Hybridization; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D051456:Gene Flow; D005787:Gene Frequency; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D006801:Humans; D008957:Models, Genetic; D009030:Mosaicism; D058885:Multilocus Sequence Typing; D009161:Mycobacterium / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial