Browsing by Author "Coscolla, M."
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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 Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans(Nature Genetics, 2013-09) Comas, I.; Coscolla, M.; Luo, T.; Borrell, S.; Holt, K.E.; Kato-Maeda, M.; Parkhill, J.; Malla, B.; Berg, S.; Thwaites, G.; Yeboah-Manu, D.; Bothamley, G.; Mei, J.; Wei, L.; Bentley, S.; Harris, S.R.; Niemann, S.; Diel, R.; Aseffa, A.; Gao, Q.; Young, D.; Gagneux, S.Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. Tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities. © 2013 Nature America, Inc. All rights reserved.Item Phylogenomics of Mycobacterium Africanum Reveals a New Lineage and a Complex Evolutionary History(microbiology research, 2021) Coscolla, M.; Gagneux, S.; Otchere, I.D.; et al.Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto, as well as two lineages (L5 and L6) traditionally referred to as Mycobacterium africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of M. africanum, and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.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 Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum(Tuberculosis, 2017-05) Ofori-Anyinam, B.; Dolganov, G.; Van, T.; Davis, J.L.; Walter, N.D.; Garcia, B.J.; Voskuil, M.; Fissette, K.; Diels, M.; Driesen, M.; Meehan, C.J.; Yeboah-Manu, D.; Coscolla, M.; Gagneux, S.; Antonio, M.; Schoolnik, G.; Gehre, F.; de Jong, B.C.Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease. © 2017 The Authors