Molecular epidemiology of Mycobacterium africanum in Ghana

Asante-Poku, Adwoa; Otchere, Isaac Darko; Osei-Wusu, Stephen; Sarpong, Esther; Forson, Audrey; Laryea, Clement; Borrell, Sònia; Bonsu, Frank; Hattendorf, Jan; Ahorlu, Collins; Koram, Kwadwo A.; Gagneux, Sébastien; Yeboah-Manu, Dorothy

doi:10.1186/s12879-016-1725-6

Cited by 42 publications

(57 citation statements)

References 36 publications

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“…Notably, a Swiss cohort study found that MTBC lineages tend to transmit preferentially among sympatric host populations[34]. Two other studies in Ghana offered a potential explanation for the geographical restriction of lineage 5 in West Africa, by showing association between these lineages and specific human ethnicities[35, 36]. A dominant lineage model of evolution can also help explain the various clinical outcomes resulting from infections with strains from distinct lineages of the MTBC.…”

Section: Discussionmentioning

confidence: 99%

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

et al. 2016

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Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis.

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Section: Discussionmentioning

confidence: 99%

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

et al. 2016

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“…We previously reported an association between L5 and Ewe patient ethnicity 9,12 . Hence to test if conservation of T cell epitopes and/or the diversity of regulatory proteins in L5 was influenced by patient ethnicity, we estimated pairwise dN/dS for sequences encoding T cell epitopes and regulatory proteins of L5 genomes stratified by patient ethnicity (Fig 7).…”

Section: Resultsmentioning

confidence: 95%

“…The delayed pro-inflammatory immune response in the “modern” MTBC lineages might allow for more rapid disease progression and transmission 17 . The second hypothesis is supported by the statistical association of L5 with the native West African ethnic group known as “Ewe” reported by two independent studies in Ghana 9,12 . The third hypothesis is mainly supported by the phylogenetic placement of Maf (L6) amidst the cluster of the animal-adapted members of the MTBC in the various phylogenies of the MTBC 5,7,18 .…”

Section: Introductionmentioning

confidence: 84%

“…Some evidence in support of the first hypothesis is the reported association of Maf (L6) with HIV co-infection, attenuated ESAT-6 responses and delayed progression to active disease relative to Mtbss 9,13–16 . In addition, both Maf lineages as well as Mtbss L1, together described as “ancestral” MTBC lineages, have been shown to elicit a stronger early production of pro-inflammatory cytokines compared to the “modern” MTBBC L2, L3 and L4 17 .…”

Section: Introductionmentioning

confidence: 86%

“…Yet the reason(s) why Maf is limited to West Africa despite, for example, centuries of the trans-Atlantic slave trade remains unknown. Some comparative studies have identified phenotypic differences between the two Maf lineage 9,10 , suggesting they might be fundamentally distinct and occupy different ecological niches.…”

Section: Introductionmentioning

confidence: 99%

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Comparative genomics ofMycobacterium africanumLineage 5 and Lineage 6 from Ghana suggests different ecological niches

Otchere

Coscollá

Sánchez-Busó

et al. 2017

Preprint

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37Mycobacterium africanum (Maf) causes up to half of human tuberculosis in West Africa, but little is 38 known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, 39 including both L5 and L6. We found that the genomic diversity of L6 was higher than in L5, and 40 the selection pressures differed between both groups. Regulatory proteins appeared to evolve 41 neutrally in L5 but under purifying selection in L6. Conversely, human T cell epitopes were under 42 purifying selection in L5, but under positive selection in L6. Although only 10% of the T cell 43 epitopes were variable, mutations were mostly lineage-specific. Our findings indicate that Maf L5 44 and L6 are genomically distinct, possibly reflecting different ecological niches. 45 46 47. CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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The Nature and Evolution of Genomic Diversity in the Mycobacterium tuberculosis Complex

Brites

Gagneux

2017

Advances in Experimental Medicine and Biology

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The Mycobacterium tuberculosis Complex (MTBC) consists of a clonal group of several mycobacterial lineages pathogenic to a range of different mammalian hosts. In this chapter, we discuss the origins and the evolutionary forces shaping the genomic diversity of the human-adapted MTBC. Advances in whole-genome sequencing have brought invaluable insights into the macro-evolution of the MTBC, and the biogeographical distribution of the different MTBC lineages, the phylogenetic relationships between these lineages. Moreover, micro-evolutionary processes start to be better understood, including those influencing bacterial mutation rates and those governing the fate of new mutations emerging within patients during treatment. Current genomic and epidemiological evidence reflect the fact that, through ecological specialization, the MTBC affecting humans became an obligate and extremely well-adapted human pathogen. Identifying the adaptive traits of human-adapted MTBC and unraveling the bacterial loci that interact with human genomic variation might help identify new targets for developing better vaccines and designing more effective treatments.

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Molecular epidemiology of Mycobacterium africanum in Ghana

Cited by 42 publications

References 36 publications

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity

Comparative genomics ofMycobacterium africanumLineage 5 and Lineage 6 from Ghana suggests different ecological niches

The Nature and Evolution of Genomic Diversity in the Mycobacterium tuberculosis Complex

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