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Yeboah-Manu, D.

Publications and source records attributed to Yeboah-Manu, D..

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Reference Set of Mycobacterium tuberculosis Clinical Strains: A tool for research and product development

The Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and various other mammals. The human-adapted members of the MTBC comprise seven phylogenetic lineages that differ in their geographical distribution. There is growing evidence that this phylogenetic diversity modulates the outcome of TB infection and disease. For decades, TB research and development has focused on the two canonical MTBC reference strains H37Rv and Erdman, both of which belong to Lineage 4. Relying on only a few laboratory-adapted strains can be misleading as study results might not be directly transferrable to clinical settings where patients are infected with a diverse array of strains, including drug-resistant variants. Here, we argue for the need to expand TB research and development by incorporating the phylogenetic diversity of the MTBC. To facilitate such work, we have assembled a group of 20 genetically well-characterized clinical strains representing the seven known human-adapted MTBC lineages. With the \"MTBC clinical strains reference set\" we aim to provide a standardized resource for the TB community. We hope it will enable more direct comparisons between studies that explore the physiology of MTBC beyond the lab strains used thus far. We anticipate that detailed phenotypic analyses of this reference strain set will increase our understanding of TB biology and assist in the development of new control tools that are universally effective.

microbiology

Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa

BackgroundUnderstanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana.\n\nMethodsMycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110 PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis.\n\nFindingsOut of 2,309 MTBC isolates, we identified 1,082 (46{middle dot}9%) single cases with 1,227 (53{middle dot}1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41{middle dot}2%. While we see no significant difference in the recent transmission rates between lineages of Mycobacterium africanum (lineage-5 (31{middle dot}8%); lineage-6 (24{middle dot}7%), p=0{middle dot}118), we found that lineage-4 belonging to the M. tuberculosis transmitted significantly higher (44{middle dot}9%, p<0{middle dot}001). Finally, apart from age being significantly associated with recent TB transmission (p=0{middle dot}007), we additionally identified a significant departure in the male/female ratio among very large clustered cases compared to the general TB patient population (3:1 vs. 2:1, p=0{middle dot}022).\n\nInterpretationsOur findings indicate high recent TB transmission suggesting occurrences of unsuspected outbreaks. The observed reduced transmission rate of M. africanum suggests other factor(s) may be responsible for its continuous presence in West Africa.\n\nFundingWellcome Trust Intermediate Fellowship Grant 097134/Z/11/Z to Dorothy Yeboah-Manu.

epidemiology

Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests different ecological niches

Mycobacterium africanum (Maf) causes up to half of human tuberculosis in West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including both L5 and L6. We found that the genomic diversity of L6 was higher than in L5, and the selection pressures differed between both groups. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Conversely, human T cell epitopes were under purifying selection in L5, but under positive selection in L6. Although only 10% of the T cell epitopes were variable, mutations were mostly lineage-specific. Our findings indicate that Maf L5 and L6 are genomically distinct, possibly reflecting different ecological niches.

genomics