Research Article: Locally Confined Clonal Complexes of Mycobacterium ulcerans in Two Buruli Ulcer Endemic Regions of Cameroon

Date Published: June 5, 2015

Publisher: Public Library of Science

Author(s): Miriam Bolz, Martin W. Bratschi, Sarah Kerber, Jacques C. Minyem, Alphonse Um Boock, Moritz Vogel, Pierre Franklin Bayi, Thomas Junghanss, Daniela Brites, Simon R. Harris, Julian Parkhill, Gerd Pluschke, Araceli Lamelas Cabello, Christian Johnson.

Abstract: BackgroundMycobacterium ulcerans is the causative agent of the necrotizing skin disease Buruli ulcer (BU), which has been reported from over 30 countries worldwide. The majority of notified patients come from West African countries, such as Côte d’Ivoire, Ghana, Benin and Cameroon. All clinical isolates of M. ulcerans from these countries are closely related and their genomes differ only in a limited number of single nucleotide polymorphisms (SNPs).Methodology/Principal FindingsWe performed a molecular epidemiological study with clinical isolates from patients from two distinct BU endemic regions of Cameroon, the Nyong and the Mapé river basins. Whole genome sequencing of the M. ulcerans strains from these two BU endemic areas revealed the presence of two phylogenetically distinct clonal complexes. The strains from the Nyong river basin were genetically more diverse and less closely related to the M. ulcerans strain circulating in Ghana and Benin than the strains causing BU in the Mapé river basin.ConclusionsOur comparative genomic analysis revealed that M. ulcerans clones diversify locally by the accumulation of SNPs. Case isolates coming from more recently emerging BU endemic areas, such as the Mapé river basin, may be less diverse than populations from longer standing disease foci, such as the Nyong river basin. Exchange of strains between distinct endemic areas seems to be rare and local clonal complexes can be easily distinguished by whole genome sequencing.

Partial Text: Buruli ulcer (BU), the third most common mycobacterial disease affecting humans after tuberculosis and leprosy, is caused by Mycobacterium ulcerans [1]. The disease is characterized by progressive necrosis of the skin and subcutaneous tissue, leading to sometimes extensive ulcerations. Even though standard antibiotic treatment for eight weeks with rifampicin and streptomycin, as it is currently recommended by the World Health Organization (WHO), is highly effective in killing the bacterium, quite a number of patients still require surgery for wound debridement and/or skin grafting and can remain with scarring and disabilities [2]. BU has been reported from over 30 countries worldwide but has its highest incidence in West Africa, where it occurs very focally in rural areas, which are associated with wetlands, marshes and riverine zones [3].

Due to the limitations of conventional typing methods for the differentiation of strains belonging to the highly monomorphic African M. ulcerans population, use of WGS was suggested to reach sufficient analytical depth for molecular epidemiology studies [32]. Here our comparative genomic analysis of strains from two geographically separated BU endemic areas of Cameroon, the Mapé and the Nyong river basins, identified two phylogenetically distinct lineages of M. ulcerans. These data support previous findings that the spread of local clonal lineages between endemic areas only rarely occurs [13,14]. In a previous IS element—SNP based typing study most strains from the central region of Cameroon had the same SNP types as strains from neighbouring Gabon. The IS element—SNP type found in a strain from the Mapé river basin was also present across entire Central and West-Africa leading to the hypothesis that this lineage represents the founder of the other observed IS element—SNP types [15]. Our WGS analysis showed that the strains from the Mapé river basin are in fact more closely related to the M. ulcerans strain circulating in Ghana and Benin than the strains belonging to the Nyong river basin lineage. Additional WGS data with strains from all BU endemic African countries are required to shed more light on the spread and evolution of M. ulcerans in Africa and the origin of the locally observed two distinct Cameroonian lineages.



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