title: Multiple Introductions and Recent Spread of the Emerging Human Pathogen Mycobacterium ulcerans across Africa.
abstract: Buruli ulcer (BU) is an insidious neglected tropical disease. Cases are reported around the world but the rural regions of West and Central Africa are most affected. How BU is transmitted and spreads has remained a mystery, even though the causative agent, Mycobacterium ulcerans, has been known for more than 70 years. Here, using the tools of population genomics, we reconstruct the evolutionary history of M. ulcerans by comparing 165 isolates spanning 48 years and representing 11 endemic countries across Africa. The genetic diversity of African M. ulcerans was found to be restricted due to the bacterium's slow substitution rate coupled with its relatively recent origin. We identified two specific M. ulcerans lineages within the African continent, and inferred that M. ulcerans lineage Mu_A1 existed in Africa for several hundreds of years, unlike lineage Mu_A2, which was introduced much more recently, approximately during the 19th century. Additionally, we observed that specific M. ulcerans epidemic Mu_A1 clones were introduced during the same time period in the three hydrological basins that were well covered in our panel. The estimated time span of the introduction events coincides with the Neo-imperialism period, during which time the European colonial powers divided the African continent among themselves. Using this temporal association, and in the absence of a known BU reservoir or-vector on the continent, we postulate that the so-called "Scramble for Africa" played a significant role in the spread of the disease across the continent.
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.|Evolutionary Ecology Group University of Antwerp, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandelannoote
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Conor J
authors.initials: CJ
authors.lastname: Meehan
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eddyani
authors.affiliation: Laboratoire de Référence des Mycobactéries, Cotonou, Benin.
authors.forename: Dissou
authors.initials: D
authors.lastname: Affolabi
authors.affiliation: Institut Médical Evangélique, Kimpese, Republic, Democratic of Congo.
authors.forename: Delphin Mavinga
authors.initials: DM
authors.lastname: Phanzu
authors.affiliation: Service de Mycobactériologie, Centre Pasteur du Cameroun, Yaoundé, Cameroun.
authors.forename: Sara
authors.initials: S
authors.lastname: Eyangoh
authors.affiliation: Evolutionary Ecology Group University of Antwerp, Antwerp, Belgium.|Invertebrates Section, Royal Museum for Central Africa, Tervuren, Belgium.
authors.forename: Kurt
authors.initials: K
authors.lastname: Jordaens
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 Microbiology and Immunology, University of Melbourne, Victoria, Australia.
authors.forename: Kirstie
authors.initials: K
authors.lastname: Mangas
authors.affiliation: Victorian Life Sciences Computation Initiative University of Melbourne, Victoria, Australia.
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.affiliation: CRCNA Inserm U892 CNRS 6299, CHU & Université d'Angers, Angers, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Marsollier
authors.affiliation: CRCNA Inserm U892 CNRS 6299, CHU & Université d'Angers, Angers, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Marion
authors.affiliation: CDTUB de Pobè, Pobè, Benin.
authors.forename: Annick
authors.initials: A
authors.lastname: Chauty
authors.affiliation: Service de Mycobactériologie, Centre Pasteur du Cameroun, Yaoundé, Cameroun.|Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Landier
authors.affiliation: Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.affiliation: Evolutionary Ecology Group University of Antwerp, Antwerp, Belgium.
authors.forename: Herwig
authors.initials: H
authors.lastname: Leirs
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
mesh_terms: D000349:Africa; D054312:Buruli Ulcer / Q000235:genetics* / Q000382:microbiology / Q000635:transmission; D019143:Evolution, Molecular; D014644:Genetic Variation; D005828:Genetics, Population; D016680:Genome, Bacterial; D006801:Humans; D019911:Mycobacterium ulcerans / Q000235:genetics* / Q000472:pathogenicity; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
keywords: bacterial pathogen transmission; microbial population genomics; molecular evolution; phylogeography