title: Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria from a common Mycobacterium marinum progenitor.
abstract: It had been assumed that production of the cytotoxic polyketide mycolactone was strictly associated with Mycobacterium ulcerans, the causative agent of Buruli ulcer. However, a recent study has uncovered a broader distribution of mycolactone-producing mycobacteria (MPM) that includes mycobacteria cultured from diseased fish and frogs in the United States and from diseased fish in the Red and Mediterranean Seas. All of these mycobacteria contain versions of the M. ulcerans pMUM plasmid, produce mycolactones, and show a high degree of genetic relatedness to both M. ulcerans and Mycobacterium marinum. Here, we show by multiple genetic methods, including multilocus sequence analysis and DNA-DNA hybridization, that all MPM have evolved from a common M. marinum progenitor to form a genetically cohesive group among a more diverse assemblage of M. marinum strains. Like M. ulcerans, the fish and frog MPM show multiple copies of the insertion sequence IS2404. Comparisons of pMUM and chromosomal gene sequences demonstrate that plasmid acquisition and the subsequent ability to produce mycolactone were probably the key drivers of speciation. Ongoing evolution among MPM has since produced at least two genetically distinct ecotypes that can be broadly divided into those typically causing disease in ectotherms (but also having a high zoonotic potential) and those causing disease in endotherms, such as humans.
authors.affiliation: Department of Microbiology, Monash University, Wellington Road, Clayton 3800, Australia.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Yip
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Porter
authors.forename: Janet A M
authors.initials: JA
authors.lastname: Fyfe
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Lavender
authors.forename: Françoise
authors.initials: F
authors.lastname: Portaels
authors.forename: Martha
authors.initials: M
authors.lastname: Rhodes
authors.forename: Howard
authors.initials: H
authors.lastname: Kator
authors.forename: Angelo
authors.initials: A
authors.lastname: Colorni
authors.forename: Grant A
authors.initials: GA
authors.lastname: Jenkin
authors.forename: Tim
authors.initials: T
authors.lastname: Stinear
mesh_terms: D001427:Bacterial Toxins / Q000096:biosynthesis*; D001483:Base Sequence; D004251:DNA Transposable Elements; D019143:Evolution, Molecular; D018942:Macrolides; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D019910:Mycobacterium marinum / Q000235:genetics* / Q000378:metabolism; D019911:Mycobacterium ulcerans / Q000235:genetics* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D017422:Sequence Analysis, DNA
chemical_list: D001427:Bacterial Toxins; D004251:DNA Transposable Elements; D018942:Macrolides; C117218:mycolactone