title: Insertion sequence element single nucleotide polymorphism typing provides insights into the population structure and evolution of Mycobacterium ulcerans across Africa.
abstract: Buruli ulcer is an indolent, slowly progressing necrotizing disease of the skin caused by infection with Mycobacterium ulcerans. In the present study, we applied a redesigned technique to a vast panel of M. ulcerans disease isolates and clinical samples originating from multiple African disease foci in order to (i) gain fundamental insights into the population structure and evolutionary history of the pathogen and (ii) disentangle the phylogeographic relationships within the genetically conserved cluster of African M. ulcerans. Our analyses identified 23 different African insertion sequence element single nucleotide polymorphism (ISE-SNP) types that dominate in different areas where Buruli ulcer is endemic. These ISE-SNP types appear to be the initial stages of clonal diversification from a common, possibly ancestral ISE-SNP type. ISE-SNP types were found unevenly distributed over the greater West African hydrological drainage basins. Our findings suggest that geographical barriers bordering the basins to some extent prevented bacterial gene flow between basins and that this resulted in independent focal transmission clusters associated with the hydrological drainage areas. Different phylogenetic methods yielded two well-supported sister clades within the African ISE-SNP types. The ISE-SNP types from the "pan-African clade" were found to be widespread throughout Africa, while the ISE-SNP types of the "Gabonese/Cameroonian clade" were much rarer and found in a more restricted area, which suggested that the latter clade evolved more recently. Additionally, the Gabonese/Cameroonian clade was found to form a strongly supported monophyletic group with Papua New Guinean ISE-SNP type 8, which is unrelated to other Southeast Asian ISE-SNP types.
authors.affiliation: Mycobacteriology Unit, Microbiology Group, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandelannoote
authors.forename: Kurt
authors.initials: K
authors.lastname: Jordaens
authors.forename: Pieter
authors.initials: P
authors.lastname: Bomans
authors.forename: Herwig
authors.initials: H
authors.lastname: Leirs
authors.forename: Lies
authors.initials: L
authors.lastname: Durnez
authors.forename: Dissou
authors.initials: D
authors.lastname: Affolabi
authors.forename: Ghislain
authors.initials: G
authors.lastname: Sopoh
authors.forename: Julia
authors.initials: J
authors.lastname: Aguiar
authors.forename: Delphin Mavinga
authors.initials: DM
authors.lastname: Phanzu
authors.forename: Kapay
authors.initials: K
authors.lastname: Kibadi
authors.forename: Sara
authors.initials: S
authors.lastname: Eyangoh
authors.forename: Louis Bayonne
authors.initials: LB
authors.lastname: Manou
authors.forename: Richard Odame
authors.initials: RO
authors.lastname: Phillips
authors.forename: Ohene
authors.initials: O
authors.lastname: Adjei
authors.forename: Anthony
authors.initials: A
authors.lastname: Ablordey
authors.forename: Leen
authors.initials: L
authors.lastname: Rigouts
authors.forename: Françoise
authors.initials: F
authors.lastname: Portaels
authors.forename: Miriam
authors.initials: M
authors.lastname: Eddyani
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000349:Africa; D054312:Buruli Ulcer / Q000453:epidemiology / Q000382:microbiology*; D016000:Cluster Analysis; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D019353:Endemic Diseases; D051456:Gene Flow; D005838:Genotype; D006801:Humans; D019911:Mycobacterium ulcerans / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide
chemical_list: D004251:DNA Transposable Elements; D004269:DNA, Bacterial