title: Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci for subtyping of Mycobacterium tuberculosis Beijing isolates.
abstract: Mycobacterium tuberculosis Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing.
authors.affiliation: Genoscreen, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Allix-Béguec
authors.forename: Céline
authors.initials: C
authors.lastname: Wahl
authors.forename: Madeleine
authors.initials: M
authors.lastname: Hanekom
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
authors.forename: Shinji
authors.initials: S
authors.lastname: Maeda
authors.forename: Isolina
authors.initials: I
authors.lastname: Campos-Herrero
authors.forename: Igor
authors.initials: I
authors.lastname: Mokrousov
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.forename: Irina
authors.initials: I
authors.lastname: Kontsevaya
authors.forename: Nalin
authors.initials: N
authors.lastname: Rastogi
authors.forename: Sofia
authors.initials: S
authors.lastname: Samper
authors.forename: Li-Hwei
authors.initials: LH
authors.lastname: Sng
authors.forename: Robin M
authors.initials: RM
authors.lastname: Warren
authors.forename: Philip
authors.initials: P
authors.lastname: Supply
mesh_terms: D006801:Humans; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics*; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology*