title: Whole genome comparisons suggest random distribution of Mycobacterium ulcerans genotypes in a Buruli ulcer endemic region of Ghana.
abstract: Efforts to control the spread of Buruli ulcer--an emerging ulcerative skin infection caused by Mycobacterium ulcerans--have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30 km2 region within the Asante Akim North District, Ashanti region, Ghana, with 15 other M. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a single M. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matched M. ulcerans from Nigeria, suggesting another introduction of M. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2 Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identical M. ulcerans genotypes but lived in geographically separate villages. We conclude that M. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time that M. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of M. ulcerans thus might include humans, or perhaps M. ulcerans-infected animals such as livestock that move regularly between countries.
authors.affiliation: Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Ablordey
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandelannoote
authors.affiliation: Department of Animal Biology and Conservation Science, University of Ghana, Accra, Ghana.
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Frimpong
authors.affiliation: Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: Evans K
authors.initials: EK
authors.lastname: Ahortor
authors.affiliation: Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors.forename: Nana Ama
authors.initials: NA
authors.lastname: Amissah
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eddyani
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: Durnez
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Portaels
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.affiliation: Department of Biology, University of Antwerp, Antwerp, Belgium.
authors.forename: Herwig
authors.initials: H
authors.lastname: Leirs
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Porter
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Kirstie M
authors.initials: KM
authors.lastname: Mangas
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Margaret M C
authors.initials: MM
authors.lastname: Lam
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Buultjens
authors.affiliation: Life Sciences Computation Centre, Victorian Life Sciences Computation Initiative, Carlton, Victoria, Australia.
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Tobias
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
mesh_terms: D054312:Buruli Ulcer / Q000453:epidemiology*; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics*; D005838:Genotype; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D019911:Mycobacterium ulcerans / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
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