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Whole genome comparisons suggest random distribution of Mycobacterium ulcerans genotypes in a Buruli ulcer endemic region of Ghana.

Ablordey AS, Vandelannoote K, Frimpong IA, Ahortor EK, Amissah NA, Eddyani M, Durnez L, Portaels F, de Jong BC, Leirs H, Porter JL, Mangas KM, Lam MM, Buultjens A, Seemann T, Tobias NJ, Stinear TP - PLoS Negl Trop Dis (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, 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.

No MeSH data available.


Related in: MedlinePlus

Genetic relationship among the 33 M. ulcerans isolates used in this study.A maximum-likelihood consensus phylogeny was inferred based on whole genome alignments of each of the isolates against the M. ulcerans Agy99 reference genome. The alignment file from pairwise comparisons of the resulting 320 variable nucleotide positions was used as input for RaxML. Nodes with less than 70% bootstrap support (1000 replicates) were collapsed.
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pntd.0003681.g001: Genetic relationship among the 33 M. ulcerans isolates used in this study.A maximum-likelihood consensus phylogeny was inferred based on whole genome alignments of each of the isolates against the M. ulcerans Agy99 reference genome. The alignment file from pairwise comparisons of the resulting 320 variable nucleotide positions was used as input for RaxML. Nodes with less than 70% bootstrap support (1000 replicates) were collapsed.

Mentions: Eighteen M. ulcerans isolates were randomly selected for whole genome sequencing. The isolates represented 20% (total of 92 isolates from 2010–2012) of all culture-confirmed BU cases referred to the Agogo Presbyterian Hospital between 2010 and 2012 (Table 1). There were no differences in colony phenotype or growth characteristics among the isolates. The DNA sequence reads for each genome were mapped to the M. ulcerans Agy99 reference sequence. Sequencing and read-mapping summary statistics are given in Table 1. In addition to the 18 Agogo isolates sequenced here, 15 other genomes (including some previously described) were included in comparisons making a total of 33 isolates (Table 1). These additional genomes were from M. ulcerans isolates in other regions of Ghana and from surrounding countries to provide appropriate genetic context for interpreting the diversity and evolution of M. ulcerans isolates from around Agogo. Read-mapping and SNP identification revealed 320 variable nucleotide positions across a 5.2Mb core genome for the 33 isolates. A phylogeny was inferred from this alignment, showing the clustering typical of M. ulcerans genotypes with geographic origin (Fig. 1). A separate SNP alignment was performed taking the genome sequences for only the 18 isolates from the Agogo region, and 10 of them (called Agogo-1) clustered with isolates from the neighboring district of Amansie West and also the Ivory Coast, the country which borders this region to the west (Fig. 1). This close relationship is indicative of a local clone that has spread and persisted within the greater region for some time. Unexpectedly however, this analysis also revealed the presence of a second distinct M. ulcerans genotype co-circulating with Agogo-1. This second genotype (called Agogo-2) was substantially more diverse from all other Ghanaian M. ulcerans genotypes (138 SNPs), suggesting the re-introduction of M. ulcerans to the Agogo region, potentially from a source outside Ghana (Fig. 1, S1 Table). The intra-genotype variation within either cluster was low. The mean nucleotide pairwise identity was 94.7% (SEM ± 0.4) for Agogo-1 versus 97.2% (SEM ± 0.4) for Agogo 2. The mean pairwise nucleotide identity was significantly lower for Agogo-2 genomes compared with Agogo-1 (p<0.001).


Whole genome comparisons suggest random distribution of Mycobacterium ulcerans genotypes in a Buruli ulcer endemic region of Ghana.

Ablordey AS, Vandelannoote K, Frimpong IA, Ahortor EK, Amissah NA, Eddyani M, Durnez L, Portaels F, de Jong BC, Leirs H, Porter JL, Mangas KM, Lam MM, Buultjens A, Seemann T, Tobias NJ, Stinear TP - PLoS Negl Trop Dis (2015)

Genetic relationship among the 33 M. ulcerans isolates used in this study.A maximum-likelihood consensus phylogeny was inferred based on whole genome alignments of each of the isolates against the M. ulcerans Agy99 reference genome. The alignment file from pairwise comparisons of the resulting 320 variable nucleotide positions was used as input for RaxML. Nodes with less than 70% bootstrap support (1000 replicates) were collapsed.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380315&req=5

pntd.0003681.g001: Genetic relationship among the 33 M. ulcerans isolates used in this study.A maximum-likelihood consensus phylogeny was inferred based on whole genome alignments of each of the isolates against the M. ulcerans Agy99 reference genome. The alignment file from pairwise comparisons of the resulting 320 variable nucleotide positions was used as input for RaxML. Nodes with less than 70% bootstrap support (1000 replicates) were collapsed.
Mentions: Eighteen M. ulcerans isolates were randomly selected for whole genome sequencing. The isolates represented 20% (total of 92 isolates from 2010–2012) of all culture-confirmed BU cases referred to the Agogo Presbyterian Hospital between 2010 and 2012 (Table 1). There were no differences in colony phenotype or growth characteristics among the isolates. The DNA sequence reads for each genome were mapped to the M. ulcerans Agy99 reference sequence. Sequencing and read-mapping summary statistics are given in Table 1. In addition to the 18 Agogo isolates sequenced here, 15 other genomes (including some previously described) were included in comparisons making a total of 33 isolates (Table 1). These additional genomes were from M. ulcerans isolates in other regions of Ghana and from surrounding countries to provide appropriate genetic context for interpreting the diversity and evolution of M. ulcerans isolates from around Agogo. Read-mapping and SNP identification revealed 320 variable nucleotide positions across a 5.2Mb core genome for the 33 isolates. A phylogeny was inferred from this alignment, showing the clustering typical of M. ulcerans genotypes with geographic origin (Fig. 1). A separate SNP alignment was performed taking the genome sequences for only the 18 isolates from the Agogo region, and 10 of them (called Agogo-1) clustered with isolates from the neighboring district of Amansie West and also the Ivory Coast, the country which borders this region to the west (Fig. 1). This close relationship is indicative of a local clone that has spread and persisted within the greater region for some time. Unexpectedly however, this analysis also revealed the presence of a second distinct M. ulcerans genotype co-circulating with Agogo-1. This second genotype (called Agogo-2) was substantially more diverse from all other Ghanaian M. ulcerans genotypes (138 SNPs), suggesting the re-introduction of M. ulcerans to the Agogo region, potentially from a source outside Ghana (Fig. 1, S1 Table). The intra-genotype variation within either cluster was low. The mean nucleotide pairwise identity was 94.7% (SEM ± 0.4) for Agogo-1 versus 97.2% (SEM ± 0.4) for Agogo 2. The mean pairwise nucleotide identity was significantly lower for Agogo-2 genomes compared with Agogo-1 (p<0.001).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, 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.

No MeSH data available.


Related in: MedlinePlus