Assessment of Mycobacterial Interspersed Repetitive Unit-QUB Markers To Further Discriminate the Beijing Genotype in a Population-Based Study of the Genetic Diversity of Mycobacterium tuberculosis Clinical Isolates from Okinawa, Ryukyu Islands, Japan
- 1 November 2007
- journal article
- Published by American Society for Microbiology in Journal of Clinical Microbiology
- Vol. 45 (11), 3606-3615
- https://doi.org/10.1128/jcm.00348-07
Abstract
The present investigation focused on genetic diversity and drug resistance of 101 Mycobacterium tuberculosis strains isolated between July 2003 and February 2005 in the Okinawa prefecture, Ryukyu Islands, Japan. A high rate of clustering (87%, eight clusters, 2 to 69 strains/cluster) was observed upon spoligotyping; most of it was due to the lower discriminatory power of this method for the Beijing lineage ( n = 72; 71.3% of the isolates). The remaining diversity was limited to seven clusters (two to five isolates/cluster), with the following distribution of major lineages: ill-defined T ( n = 13; 12.8%), ancestral East African-Indian ( n = 6; 5.9%), Haarlem ( n = 4; 4%), Latin American-Mediterranean ( n = 2; 2%), X1 ( n = 1; 1%), and a total absence of the central Asian clade. Three remaining strains could not be classified on the basis of their spoligotype pattern and were labeled “unknown.” Subtyping with mycobacterial interspersed repetitive units (MIRUs) in association with additional QUB minisatellites was performed to discriminate among the Beijing strains. Based on an “in-house” spoligotyping/MIRU database ( n = 694 Beijing strains), eight highly discriminative MIRU loci for Beijing strains were selected (loci numbered 10, 16, 23, 26, 27, 31, 39, and 40). The highest discriminatory power ( h ) observed in our sample ( n = 72; M-26, 0.385; M-10, 0.38; M-31, 0.255; M-16, 0.238) was too low, and 73.6% of the Beijing strains from Okinawa remained clustered. Typing of Beijing strains with additional QUB loci (with the exception of “one-copy” QUB-1451) resulted in higher discriminatory powers: QUB-11b, 0.68; QUB-11a, 0.656; QUB-26, 0.644; QUB-18, 0.553; QUB-4156, 0.5; and QUB-1895, 0.453. A definitive algorithm on the use of QUB markers to subtype Beijing isolates in expanded studies would shed light on their hypervariability, which may sometimes blur recognition between epidemiologically linked Beijing isolates. The total absence of multiple drug resistance among Beijing isolates from Okinawa, as well as the relatively older ages of the patients (majority above 60 years), shows that tuberculosis (TB) is a declining disease in Okinawa, and an adequate TB control program has successfully avoided both the emergence and the spread of multidrug-resistant TB in this insular setting.Keywords
This publication has 36 references indexed in Scilit:
- Proposal for Standardization of Optimized Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing ofMycobacterium tuberculosisJournal of Clinical Microbiology, 2006
- Differentiation of Tuberculosis Strains in a Population with Mainly Beijing-family StrainsEmerging Infectious Diseases, 2006
- Beijing/W GenotypeMycobacterium tuberculosisand Drug ResistanceEmerging Infectious Diseases, 2006
- Optimization of variable number tandem repeat typing set for differentiating Mycobacterium tuberculosis strains in the Beijing familyFEMS Microbiology Letters, 2006
- Comparison of drug resistance genotypes between Beijing and non-Beijing family strains of Mycobacterium tuberculosis in KoreaJournal of Microbiological Methods, 2005
- Molecular Typing ofMycobacterium tuberculosisby Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Analysis, a More Accurate Method for Identifying Epidemiological Links between Patients with TuberculosisJournal of Clinical Microbiology, 2005
- Utility of Mycobacterial Interspersed Repetitive Unit Typing for Differentiating Multidrug-ResistantMycobacterium tuberculosisIsolates of the Beijing FamilyJournal of Clinical Microbiology, 2005
- Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence areaMolecular Microbiology, 2003
- Mycobacterium tuberculosisIsolates of Beijing Genotype in ThailandEmerging Infectious Diseases, 2001
- Mycobacterium tuberculosis Beijing Genotype Emerging in VietnamEmerging Infectious Diseases, 2000