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Proficient Detection of Multi-Drug-Resistant Mycobacterium tuberculosis by Padlock Probes and Lateral Flow Nucleic Acid Biosensors
Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden.;Res Ctr Borstel, Mol & Expt Mycobacteriol, Borstel, Germany..
Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden.;Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China..
Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-10691 Stockholm, Sweden..
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2016 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 8, 4277-4284 p.Article in journal (Refereed) PublishedText
Abstract [en]

Tuberculosis is a major communicable disease. Its causative agent, Mycobacterium tuberculosis, becomes resistant to antibiotics by acquisition of point mutations in the chromosome. Multi-drug-resistant tuberculosis (MDR-TB) is an increasing public health threat, and prompt detection of such strains is of critical importance. As rolling circle amplification of padlock probes can be used to robustly distinguish single-nucleotide variants, we combined this technique with a sensitive lateral flow nucleic acid biosensor to develop a rapid molecular diagnostic test for MDR-TB, A proof-of-concept test was established for detection of the most common mutations [rpoB 531 (TCG/TTG) and katG 315 (AGC/ACC)] causing MDR-TB and verification of loss of the respective wild type. The molecular diagnostic test produces visual signals corresponding to the respective genotypes on lateral flow strips in approximately 75 min. By detecting only two mutations, the test can detect about 60% of all MDR-TB cases. The padlock probe-lateral flow (PLP-LF) test is the first of its kind and can ideally be performed at resource-limited clinical laboratories. Rapid information about the drug-susceptibility pattern can assist clinicians to choose suitable treatment regimens and take appropriate infection control actions rather than prescribing empirical treatment, thereby helping to control the spread of MDR-TB in the community.

Place, publisher, year, edition, pages
2016. Vol. 88, no 8, 4277-4284 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-297907DOI: 10.1021/acs.analchem.5b04312ISI: 000374706000018PubMedID: 26985774OAI: oai:DiVA.org:uu-297907DiVA: diva2:944283
Funder
Swedish Research CouncilVINNOVAEU, European Research Council
Available from: 2016-06-29 Created: 2016-06-28 Last updated: 2016-06-29Bibliographically approved

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Engström, Anna
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Department of Medical Biochemistry and Microbiology
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Analytical Chemistry
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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