Multiplex Detection Of Extensively Drug Resistant Tuberculosis Using Binary Deoxyribozyme Sensors

Keywords

Binary deoxyribozyme; Diagnostics; Drug resistance; Multiplex PCR; Nucleic acid sensors; Tuberculosis

Abstract

Current diagnostic tools for Mycobacterium tuberculosis (Mtb) have many disadvantages including low sensitivity, slow turnaround times, or high cost. Accurate, easy to use, and inexpensive point of care molecular diagnostic tests are urgently needed for the analysis of multidrug resistant (MDR) and extensively drug resistant (XDR) Mtb strains that emerge globally as a public health threat. In this study, we established proof-of-concept for a novel diagnostic platform (TB-DzT) for Mtb detection and the identification of drug resistant mutants using binary deoxyribozyme sensors (BiDz). TB-DzT combines a multiplex PCR with single nucleotide polymorphism (SNP) detection using highly selective BiDz sensors targeting loci associated with species typing and resistance to rifampin, isoniazid and fluoroquinolone antibiotics. Using the TB-DzT assay, we demonstrated accurate detection of Mtb and 5 mutations associated with resistance to three anti-TB drugs in clinical isolates. The assay also enables detection of a minority population of drug resistant Mtb, a clinically relevant scenario referred to as heteroresistance. Additionally, we show that TB-DzT can detect the presence of unknown mutations at target loci using combinatorial BiDz sensors. This diagnostic platform provides the foundation for the development of cost-effective, accurate and sensitive alternatives for molecular diagnostics of MDR- and XDR-TB.

Publication Date

8-15-2017

Publication Title

Biosensors and Bioelectronics

Volume

94

Number of Pages

176-183

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bios.2017.02.051

Socpus ID

85014725651 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85014725651

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