title: Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria.
abstract: Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of dominant lineages remains a matter of debate. Here, by using fluorescence-assisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade. We found that the obtained recombinants had received multiple donor-derived DNA fragments in the size range of 100 bp to 118 kbp, fragments large enough to contain whole operons. Although the transfer frequency between M. canettii strains was low and no transfer could be observed among classical Mycobacterium tuberculosis complex (MTBC) strains, our study provides the proof of concept for genetic exchange in tubercle bacilli. This outstanding, now experimentally validated phenomenon presumably played a key role in the early evolution of the MTBC toward pathogenicity. Moreover, our findings also provide important information for the risk evaluation of potential transfer of drug resistance and fitness mutations among clinically relevant mycobacterial strains.
authors.affiliation: Institut Pasteur (IP), Unit for Integrated Mycobacterial Pathogenomics, 75015 Paris, France;
authors.forename: Eva C
authors.initials: EC
authors.lastname: Boritsch
authors.affiliation: IP, Hub Bioinformatique et Biostatistique, C3BI, Unité de Services et de Recherche, USR 3756, IP CNRS, 75015 Paris, France;
authors.forename: Varun
authors.initials: V
authors.lastname: Khanna
authors.affiliation: Institut Pasteur (IP), Unit for Integrated Mycobacterial Pathogenomics, 75015 Paris, France;
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pawlik
authors.affiliation: Institut Pasteur (IP), Unit for Integrated Mycobacterial Pathogenomics, 75015 Paris, France;
authors.forename: Nadine
authors.initials: N
authors.lastname: Honoré
authors.affiliation: IP, Lymphocyte Cell Biology Unit, 75015 Paris, France;
authors.forename: Victor H
authors.initials: VH
authors.lastname: Navas
authors.affiliation: IP, PF1-Plate-Forme Génomique, 75015 Paris, France;
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.affiliation: IP, PF1-Plate-Forme Génomique, 75015 Paris, France;
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.affiliation: Victorian Life Sciences Computation Initiative, University of Melbourne, Carlton, VIC 3053, Australia;
authors.forename: Torsten
authors.identifier: 0000-0001-6046-610X
authors.initials: T
authors.lastname: Seemann
authors.affiliation: INSERM U1019, CNRS UMR 8204, Center for Infection and Immunity, Institut Pasteur de Lille, Université de Lille, 59000 Lille, France;
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
authors.forename: Timothy P
authors.identifier: 0000-0003-0150-123X
authors.initials: TP
authors.lastname: Stinear
authors.affiliation: Institut Pasteur (IP), Unit for Integrated Mycobacterial Pathogenomics, 75015 Paris, France; roland.brosch@pasteur.fr.
authors.forename: Roland
authors.identifier: 0000-0003-2587-3863
authors.initials: R
authors.lastname: Brosch
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D009161:Mycobacterium / Q000145:classification / Q000235:genetics* / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics / Q000502:physiology; D013045:Species Specificity; D014376:Tuberculosis / Q000382:microbiology; D000073336:Whole Genome Sequencing / Q000379:methods
chemical_list: D004269:DNA, Bacterial
keywords: DNA transfer; Mycobacterium canettii; evolution; recombination; tuberculosis