Browsing by Author "Brites, D."
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Item Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests distinct ecological niches(Scientific Reports, 2018-07) Otchere, I.D.; Coscollá, M.; Sánchez-Busó, L.; Asante-Poku, A.; Brites, D.; Loiseau, C.; Meehan, C.; Osei-Wusu, S.; Forson, A.; Laryea, C.et.al.Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.Item Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean Rim[version 1; peer review: 3 approved](F1000Research, 2021) Menardo, F.; Rutaihwa, L.K.; Zwyer, M.; Borrell, S.; Comas, I.; Conceição, E.C.; Coscolla, M.; Cox, H.; Joloba, M.; Dou, H.; Feldmann, J.; Fenner, L.; Fyfe, J.; Gao, Q.; de Viedma, D.G.; Garcia-Basteiro, A.L.; Gygli, S.M.; Hella, J.; Hiza, H.; Jugheli, L.; Kamwela, L.; Kato-Maeda, M.; Liu, Q.; Ley, S.D.; Loiseau, C.; Mahasirimongkol, S.; Malla, B.; Palittapongarnpim, P.; Rakotosamimanana, N.; Rasolofo, V.; Reinhard, M.; Reither, K.; Sasamalo, M.; Duarte, R.S.; Sola, C.; Suffys, P.; Lima, K.V.B.; Yeboah-Manu, D.; Beisel, C.; Brites, D.; Gagneux, S.Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics . For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans.Item Reference set of Mycobacterium tuberculosis clinical strains: A tool for research and product development(PLoS ONE, 2019-03) Borrell, S.; Trauner, A.; Brites, D.; Rigouts, L.; Loiseau, C.; Coscolla, M.; Niemann, S.; De Jong, B.; Yeboah-Manu, D.; Kato-Maeda, M.; Feldmann, J.; Reinhard, M.; Beisel, C.; Gagneux, S.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 transferable 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.Item Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana(Frontiers in Medicine, 2020-05-19) Asare, P.; Otchere, I.D.; Bedeley, E.; Brites, D.; Loiseau, C.; Baddoo, N.A.; Asante-Poku, A.; Osei-Wusu, S.; Prah, D.A.; Borrell, S.; Reinhard, M.; Forson, A.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of Mycobacterium tuberculosis complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4–12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB.