  Research articleMycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiologyKarine Brudey1 1Unité de la Tuberculose et des Mycobactéries, Institut Pasteur de Guadeloupe, Guadeloupe 2Wadsworth Center, New York State Dept. of Health, Albany, NY, USA 3Mycobacteriology Unit, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium 4Dept. Hygiene Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria 5Dept of Infectious Diseases, Institut of Infectious Diseases, Milano, Italy 6Department of Comparative Medicine, King Faisal specialist Hospital and Research Center, Riyadh, Saudi Arabia 7Laboratoire de la Tuberculose, Institut Pasteur de Bruxelles, Belgique 8Universidad Centrooccidental Lisandro Alvarado, Barquisimeto, Venezuela and Universidad de Zaragoza, Spain 9All India Institute of Medical Sciences, New Delhi, India 10Biomedical Research and Study Center, Riga, Latvia 11Institut for Hygiene, Microbiologie and Tropical Medicine, Austria 12Universidade Federal do Rio Grande de Soul, Brazil 13Instituto de Biotecnologia INTA, Castelar, Argentina 14Dept of Medical Microbiology and Pathology, faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, School of Public Health 15University of Düsseldorf, Heinrich-Heine-University, Düsseldorf 16Dept of Internal Medicine II, University of Regensbourg, Germany 17Public Health Laboratory, Hearltlands Hospital, Birmingham, UK 18Dept of Clinical Microbiology and Infectious Diseases, Hospital Gregorio Marañon, Madrid, Spain 19Dept. of Experimental Pathology, Medical Biotechnology, Infection and Epidemiology, Pisa University, Pisa, Italy 20Laboratory of Molecular Biology applied to Mycobacteria, Dept. Mycobacteriosis, Oswaldo Cruz Institute, Rio de Janeiro, Brazil 21Centre National de Référence des Mycobactéries, Institut Pasteur, Paris, France 22MRC Centre for Molecular and Cellular Biology, Dept of medical Biochemistry, University of Stellenbosch, Tygerberg, South Africa 23Laboratory Nuclear Medicine Section, Isotope group, Bhabha Atomic Research Centre c/T.M.H. Annexe, Parel, Mumbai-400012, India 24Public Health Research Institute, Newark, NJ, USA 25Mycobacteria reference unit, Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute of Public Health and the Environment, Bilthoven, The Netherlands 26Municipal Institute of Hygiene, Prague, Czech Republic 27Statens Serum Institute, Int. Ref. lab. for Mycobacteriology, Copenhagen Denmark 28Institute of Hygiene and Epidemiology, Hanoi, Vietnam 29Universidad de Zaragoza, Zaragoza, Spain 30Laboratoire de Bactério-virologie-hygiène, CHU Dupuytren, Limoges, France 31Institut Pasteur de Saint-Petersbourg, Saint Petersbourg, Russia 32Bavarian Health and Food Safety Authority, Oberschleissheim, Germany 33Forschungszentrum, National Reference Center for Mycobacteria, Borstel, Germany 34Dept of Clinical Pathology, Padjadjaran University, Dr. Hasan Sadikin Hospital, Bandung, Indonesia 35Tuberculosis Laboratory, International Centre for Diarrhoeal Research, Dhaka, Bangladesh 36Institut Pasteur de Madagascar, Tananarive, Madagascar 37Dept of Genetics of Microorganisms, University of Lódz, Lodz, Poland 38Servicio Microbiología, Hospital Universitario Miguel Servet, Zaragoza, Spain 39State Research Center for Applied Microbiology, Obolensk, Russian Federation 40Dept. of Respiratory Medicine School of Medicine Semmelweis University, Budapest, Hungary 41Veterinary Sciences Division, Department of agriculture for Northern Ireland, Belfast, UK 42Centro regionale di Riferimento per i Micobatteri, Laboratorio de Microbiologia e Virologia, Ospedale Careggi, Firenze, Italy
BMC Microbiology 2006, 6:23doi:10.1186/1471-2180-6-23
AbstractBackgroundThe 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. ResultsThe 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. ConclusionOur 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. |
|
|
|
 |  | Log on / register Feedback | Support | My details |
on Google Scholar
author email
corresponding author email|
|
| © 1999-2008 BioMed Central Ltd unless otherwise stated |