title: Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer.
abstract: Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in humans, a neglected but devastating necrotic disease of subcutaneous tissue that is rampant throughout West and Central Africa. Here, we report the complete 5.8-Mb genome sequence of M. ulcerans and show that it comprises two circular replicons, a chromosome of 5632 kb and a virulence plasmid of 174 kb. The plasmid is required for production of the polyketide toxin mycolactone, which provokes necrosis. Comparisons with the recently completed 6.6-Mb genome of Mycobacterium marinum revealed >98% nucleotide sequence identity and genome-wide synteny. However, as well as the plasmid, M. ulcerans has accumulated 213 copies of the insertion sequence IS2404, 91 copies of IS2606, 771 pseudogenes, two bacteriophages, and multiple DNA deletions and rearrangements. These data indicate that M. ulcerans has recently evolved via lateral gene transfer and reductive evolution from the generalist, more rapid-growing environmental species M. marinum to become a niche-adapted specialist. Predictions based on genome inspection for the production of modified mycobacterial virulence factors, such as the highly abundant phthiodiolone lipids, were confirmed by structural analyses. Similarly, 11 protein-coding sequences identified as M. ulcerans-specific by comparative genomics were verified as such by PCR screening a diverse collection of 33 strains of M. ulcerans and M. marinum. This work offers significant insight into the biology and evolution of mycobacterial pathogens and is an important component of international efforts to counter Buruli ulcer.
authors.affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 75725 Paris Cedex 15, France.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.forename: Sacha
authors.initials: S
authors.lastname: Pidot
authors.forename: Wafa
authors.initials: W
authors.lastname: Frigui
authors.forename: Gilles
authors.initials: G
authors.lastname: Reysset
authors.forename: Thierry
authors.initials: T
authors.lastname: Garnier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Meurice
authors.forename: David
authors.initials: D
authors.lastname: Simon
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.forename: Magali
authors.initials: M
authors.lastname: Tichit
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Porter
authors.forename: Janine
authors.initials: J
authors.lastname: Ryan
authors.forename: Paul D R
authors.initials: PD
authors.lastname: Johnson
authors.forename: John K
authors.initials: JK
authors.lastname: Davies
authors.forename: Grant A
authors.initials: GA
authors.lastname: Jenkin
authors.forename: Pamela L C
authors.initials: PL
authors.lastname: Small
authors.forename: Louis M
authors.initials: LM
authors.lastname: Jones
authors.forename: Fredj
authors.initials: F
authors.lastname: Tekaia
authors.forename: Françoise
authors.initials: F
authors.lastname: Laval
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000222:Adaptation, Physiological; D002876:Chromosomes, Bacterial / Q000235:genetics; D004251:DNA Transposable Elements; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009160:Mycobacteriophages / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology; D019910:Mycobacterium marinum / Q000235:genetics; D019911:Mycobacterium ulcerans / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology* / Q000821:virology; D011544:Pseudogenes; D012883:Skin Ulcer / Q000382:microbiology; D013045:Species Specificity; D014774:Virulence / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements