Ultrasensitive detection of Mycobacterium tuberculosis by a rapid and specific probe-triggered one-step, simultaneous DNA hybridization and isothermal amplification combined with a lateral flow dipstick

Sci Rep. 2020 Oct 12;10(1):16976. doi: 10.1038/s41598-020-73981-6.

Abstract

Mycobacterium tuberculosis (Mtb) is an insidious scourge that has afflicted millions of people worldwide. Although there are many rapid methods to detect it based on loop-mediated isothermal amplification (LAMP) and a lateral flow dipstick (LFD), this study made further improvements using a new set of primers to enhance LAMP performance and a novel DNA probe system to simplify detection and increase specificity. The new probe system eliminates the post-LAMP hybridization step typically required for LFD assays by allowing co-hybridization and amplification of target DNA in one reaction while preventing self-polymerization that could lead to false-positive results. The improved assay was named Probe-Triggered, One-Step, Simultaneous DNA Hybridization and LAMP Integrated with LFD (SH-LAMP-LFD). SH-LAMP-LFD was simpler to perform and more sensitive than previously reported LAMP-LFD and PCR methods by 100 and 1000 times, respectively. It could detect a single cell of Mtb. The absence of cross-reactivity with 23 non-TB bacteria, and accurate test results with all 104 blind clinical samples have highlighted its accuracy. Its robustness and portability make SH-LAMP-LFD suitable for users in both low and high resource settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Probes
  • DNA, Bacterial*
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification*
  • Nucleic Acid Amplification Techniques / methods*
  • Nucleic Acid Hybridization / methods*
  • Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Tuberculosis / diagnosis*
  • Tuberculosis / microbiology*

Substances

  • DNA Probes
  • DNA, Bacterial

Supplementary concepts

  • LAMP assay