Browsing by Author "Kremer, Kristin"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Mycobacterium tuberculosis complex genetic diversity : mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology
    (2006-03) Brudey, Karine; Driscoll, Jeffrey R.; Rigouts, Leen; Prodinger, Wolfgang M.; Gori, Andrea; Al-Hajoj, Sahal A. M.; Allix, Caroline; Aristimuno, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T.; Fauville-Dufaux, Maryse; Ferdinand, Severine; Garcia de Viedma, Dario; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M.; Gutierrez, M. Cristina; Hawkey, Peter M.; Van Helden, Paul D.; Kadival, Gurujaj V.; Kreiswirth, Barry N.; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P.; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaia, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Mohammad Z.; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M. Lucia; Rusch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor; Singh, Urvashi B.; Somoskovi, Akos; Skuce, Robin; Van Soolingen, Dick; Streicher, Elizabeth M.; Suffys, Philip N.; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Veronique; Victor, Tommie C.; Warren, Robin; Yap, Sook Fan; Zaman, Kadiza; Portaels, Francoise; Rastogi, Nalin; Sola, Christophe
    Background: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.
  • Thumbnail Image
    Item
    Phylogeny of Mycobacterium tuberculosis Beijing strains constructed from Polymorphisms in genes involved in DNA replication, recombination and repair
    (Public Library of Science (PLOS), 2011-01) Mestre, Olga; Luo, Tao; Dos Vultos, Tiago; Kremer, Kristin; Murray, Alan; Namouchi, Amine; Jackson, Celine; Rauzier, Jean; Bifani, Pablo; Warren, Rob; Rasolofo, Voahangy; Mei, Jian; Gao, Qian; Gicquel, Brigitte
    Background: The Beijing family is a successful group of M. tuberculosis strains, often associated with drug resistance and widely distributed throughout the world. Polymorphic genetic markers have been used to type particular M. tuberculosis strains. We recently identified a group of polymorphic DNA repair replication and recombination (3R) genes. It was shown that evolution of M. tuberculosis complex strains can be studied using 3R SNPs and a high-resolution tool for strain discrimination was developed. Here we investigated the genetic diversity and propose a phylogeny for Beijing strains by analyzing polymorphisms in 3R genes. Methodology/Principal Findings: A group of 3R genes was sequenced in a collection of Beijing strains from different geographic origins. Sequence analysis and comparison with the ones of non-Beijing strains identified several SNPs. These SNPs were used to type a larger collection of Beijing strains and allowed identification of 26 different sequence types for which a phylogeny was constructed. Phylogenetic relationships established by sequence types were in agreement with evolutionary pathways suggested by other genetic markers, such as Large Sequence Polymorphisms (LSPs). A recent Beijing genotype (Bmyc10), which included 60% of strains from distinct parts of the world, appeared to be predominant. Conclusions/Significance: We found SNPs in 3R genes associated with the Beijing family, which enabled discrimination of different groups and the proposal of a phylogeny. The Beijing family can be divided into different groups characterized by particular genetic polymorphisms that may reflect pathogenic features. These SNPs are new, potential genetic markers that may contribute to better understand the success of the Beijing family. © 2011 Mestre et al.
  • Thumbnail Image
    Item
    SNP/RD typing of Mycobacterium tuberculosis Beijing strains reveals local and worldwide disseminated clonal complexes
    (Public Library of Science, 2011-12-05) Schurch, Anita C.; Kremer, Kristin; Hendriks, Amber C. A.; Freyee, Benthe; McEvoy, Christopher R. E.; Van Crevel, Reinout; Boeree, Martin J.; Van Helden, Paul; Warren, Robin M.; Siezen, Roland J.; Van Soolingen, Dick
    The Beijing strain is one of the most successful genotypes of Mycobacterium tuberculosis worldwide and appears to be highly homogenous according to existing genotyping methods. To type Beijing strains reliably we developed a robust typing scheme using single nucleotide polymorphisms (SNPs) and regions of difference (RDs) derived from whole-genome sequencing data of eight Beijing strains. SNP/RD typing of 259 M. tuberculosis isolates originating from 45 countries worldwide discriminated 27 clonal complexes within the Beijing genotype family. A total of 16 Beijing clonal complexes contained more than one isolate of known origin, of which two clonal complexes were strongly associated with South African origin. The remaining 14 clonal complexes encompassed isolates from different countries. Even highly resolved clonal complexes comprised isolates from distinct geographical sites. Our results suggest that Beijing strains spread globally on multiple occasions and that the tuberculosis epidemic caused by the Beijing genotype is at least partially driven by modern migration patterns. The SNPs and RDs presented in this study will facilitate future molecular epidemiological and phylogenetic studies on Beijing strains.