Proficient Detection of Multi-Drug-Resistant Mycobacterium tuberculosis by Padlock Probes and Lateral Flow Nucleic Acid Biosensors
- 4 April 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in Analytical Chemistry
- Vol. 88 (8), 4277-4284
- https://doi.org/10.1021/acs.analchem.5b04312
Abstract
Tuberculosis is a major communicable disease. Its causative agent, Mycobacterium tuberculosis, becomes resistant to antibiotics by acquisition of point mutations in the chromosome. Multidrug-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.Keywords
Funding Information
- Vetenskapsrådet
- European Commission (115153)
- VINNOVA (2013-04626)
- European Federation of Pharmaceutical Industries and Associations (115153)
This publication has 26 references indexed in Scilit:
- Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statementThe International Journal of Tuberculosis and Lung Disease, 2016
- Tuberculosis Diagnostics in 2015: Landscape, Priorities, Needs, and ProspectsThe Journal of Infectious Diseases, 2015
- The diagnostic accuracy of the GenoType®MTBDRslassay for the detection of resistance to second-line anti-tuberculosis drugsPublished by Wiley ,2014
- Gold nanoparticle based Tuberculosis immunochromatographic assay: The quantitative ESE Quanti analysis of the intensity of test and control linesBiosensors and Bioelectronics, 2014
- Rapid Diagnosis of Mycobacterium tuberculosis Infection and Drug Susceptibility TestingArchives of Pathology & Laboratory Medicine, 2013
- Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient TechnologyJournal of Clinical Microbiology, 2010
- Disposable Nucleic Acid Biosensors Based on Gold Nanoparticle Probes and Lateral Flow StripAnalytical Chemistry, 2009
- Evaluation of the GenoType MTBDRplus Assay for Rifampin and Isoniazid Susceptibility Testing of Mycobacterium tuberculosis Strains and Clinical SpecimensJournal of Clinical Microbiology, 2007
- Drug-susceptibility testing in tuberculosis: methods and reliability of resultsEuropean Respiratory Journal, 2005
- Molecular genetic basis of antimicrobial agent resistance inMycobacterium tuberculosis: 1998 updateTubercle and Lung Disease, 1998