title: Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis.
abstract: Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa. Here, we sequenced and analyzed the whole genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5× coverage), 454/Roche (13-18× coverage) and/or Illumina DNA sequencing (45-105× coverage). We show that STB isolates are highly recombinogenic and evolutionarily early branching, with larger genome sizes, higher rates of genetic variation, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse infection experiments showed that STB strains are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral STB-like pool of mycobacteria by gain of persistence and virulence mechanisms, and we provide insights into the molecular events involved.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM U1019, Center for Infection and Immunity of Lille, Lille, France. philip.supply@ibl.fr
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
authors.forename: Michael
authors.initials: M
authors.lastname: Marceau
authors.forename: Sophie
authors.initials: S
authors.lastname: Mangenot
authors.forename: David
authors.initials: D
authors.lastname: Roche
authors.forename: Carine
authors.initials: C
authors.lastname: Rouanet
authors.forename: Varun
authors.initials: V
authors.lastname: Khanna
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Alexis
authors.initials: A
authors.lastname: Criscuolo
authors.forename: Julien
authors.initials: J
authors.lastname: Tap
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pawlik
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Mickael
authors.initials: M
authors.lastname: Orgeur
authors.forename: Michel
authors.initials: M
authors.lastname: Fabre
authors.forename: Cécile
authors.initials: C
authors.lastname: Parmentier
authors.forename: Wafa
authors.initials: W
authors.lastname: Frigui
authors.forename: Roxane
authors.initials: R
authors.lastname: Simeone
authors.forename: Eva C
authors.initials: EC
authors.lastname: Boritsch
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.forename: Eve
authors.initials: E
authors.lastname: Willery
authors.forename: Danielle
authors.initials: D
authors.lastname: Walker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Grégory
authors.initials: G
authors.lastname: Salvignol
authors.forename: Fadel
authors.initials: F
authors.lastname: Sayes
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cascioferro
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.forename: Valérie
authors.initials: V
authors.lastname: Barbe
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Gutierrez
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.forename: Claudine
authors.initials: C
authors.lastname: Médigue
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cruveiller
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D019143:Evolution, Molecular; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics; D055029:Inverted Repeat Sequences / Q000235:genetics; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013154:Spleen / Q000821:virology; D014774:Virulence