Browsing by Author "Malla, B."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
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 Two new rapid SNP-typing methods for classifying mycobacterium tuberculosis complex into the main phylogenetic lineages(PLoS ONE, 2012) Stucki, D.; Malla, B.; Hostettler, S.; Huna, T.; Feldmann, J.; Yeboah-Manu, D.; Gagneux, S.There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the “Beijing” sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive