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J Clin Microbiol. 2017 Apr;55(4):1066-1073. doi: 10.1128/JCM.01662-16. Epub 2017 Jan 18.

FIND Tuberculosis Strain Bank: a Resource for Researchers and Developers Working on Tests To Detect Mycobacterium tuberculosis and Related Drug Resistance.

Author information

1
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
2
Department of Medical Microbiology, University of Gondar, Gondar, Ethiopia.
3
Universidad Peruana Cayetano Heredia, Lima, Peru.
4
Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
5
National Reference TB Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova.
6
National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia.
7
Foundation for Innovative New Diagnostics, Geneva, Switzerland david.dolinger@finddx.org.

Abstract

The spread of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB hampers global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well-characterized strains and samples from drug-resistant tuberculosis patients are necessary. In this project, the Foundation for Innovative New Diagnostics (FIND) has focused on the collection, characterization, and storage of such well-characterized reference materials and making them available to researchers and developers. The collection is being conducted at multiple centers in Southeast Asia, South America, Eastern Europe, and soon the sub-Saharan Africa regions. Strains are characterized for their phenotypic resistances and MICs to first-line drugs (FLDs) and second-line drugs (SLDs) using the automated MGIT 960 system following validated procedures and WHO criteria. Analysis of resistance-associated mutations is done by whole-genome sequencing (WGS) using the Illumina NextSeq system. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat analysis and WGS are used to determine strain lineages. All strains are maintained frozen at -80°C ± 10°C as distinct mother and daughter lots. All strains are extensively quality assured. The data presented here represent an analysis of the initial part of the collection. Currently, the bank contains 118 unique strains with extracted genomic DNA and matched sputum, serum, and plasma samples and will be expanded to a minimum of 1,000 unique strains over the next 3 years. Analysis of the current strains by phenotypic resistance testing shows 102 (86.4%), 10 (8.5%), and 6 (5.1%) MDR, XDR, and mono/poly resistant strains, respectively. Two of the strains are resistant to all 11 drugs that were phenotypically tested. WGS mutation analysis revealed FLD resistance-associated mutations in the rpoB, katG, inhA, embB, embA, and pncA genes; SLD resistance in the gyrA, gyrB, rrs, eis, and tlyA genes; and ethionamide resistance in the ethA genes. Most important lineages are represented in the bank, and further collections have been initiated to increase geographic and lineage diversity. The bank provides highly characterized and high-quality strains as a resource for researchers and developers in support of the development and evaluation of new diagnostics and drug resistance detection tools.

KEYWORDS:

diagnostics development; drug-resistant tuberculosis; strain bank

PMID:
28100602
PMCID:
PMC5377833
DOI:
10.1128/JCM.01662-16
[Indexed for MEDLINE]
Free PMC Article

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