Data mining of Mycobacterium tuberculosis complex genotyping results using mycobacterial interspersed repetitive units validates the clonal structure of spoligotyping-defined families.

Recently, a combination of spoligotyping and bioinformatics was proposed as a potential tool for defining major circulating clades of tuberculosis bacilli. In the present study, we attempted to validate the above mentioned classification using a new high-throughput marker, named mycobacterial interspersed repetitive units (MIRUs). Using 12 MIRU loci and spoligotyping, we performed data mining of results on clinical isolates of the Mycobacterium tuberculosis complex representative of global mycobacterial allelic diversity. Knowledge rules permitting automatic labeling of major M. tuberculosis families were defined. Using this strategy, MIRU 24 appeared to be most appropriate for classifying our dataset. The Bovis family was shown to be perfectly classified by a maximum of 3 MIRUs, followed by Africanum and East African Indian (EAI) families by 4 MIRUs, the Beijing family by 6 MIRUs, Haarlem and X families by 8 MIRUs, the T family by 9, and the Latin-American and Mediterranean (LAM) family by 10 MIRUs. Considering the hierarchy of family divergence, our results corroborate a recent suggestion that EAI is the ancestral family followed by Africanum and Bovis. On the other hand, T, X, LAM and Haarlem families appear to be of more recent evolution. These results indicate that data mining of MIRUs is a valuable new tool for analyzing the evolutionary dynamics of the M. tuberculosis complex, and for monitoring an infectious disease such as tuberculosis.

Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

Global distribution of Mycobacterium tuberculosis spoligotypes.

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11708 patterns from as many clinical isolates originating from more than 90 countries. The 11708 spoligotypes were clustered into 813 shared types. A total of 1300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.