2. Academic Validation
  3. A Far-Red Molecular Rotor Fluorogenic Trehalose Probe for Live Mycobacteria Detection and Drug-Susceptibility Testing

A Far-Red Molecular Rotor Fluorogenic Trehalose Probe for Live Mycobacteria Detection and Drug-Susceptibility Testing

  • Angew Chem Int Ed Engl. 2023 Jan 9;62(2):e202213563. doi: 10.1002/anie.202213563.
Nicholas Banahene 1 2,  Dana M Gepford 1,  Kyle J Biegas 1 2,  Daniel H Swanson 1,  Yen-Pang Hsu 3,  Brennan A Murphy 4,  Zachary E Taylor 4,  Irene Lepori 5,  M Sloan Siegrist 5 6,  Andrés Obregón-Henao 7,  Michael S Van Nieuwenhze 3 4,  Benjamin M Swarts 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA.
  • 2 Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA.
  • 3 Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA.
  • 4 Department of Chemistry, Indiana University, Bloomington, IN, USA.
  • 5 Department of Microbiology, University of Massachusetts, Amherst, MA, USA.
  • 6 Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.
  • 7 Department of Microbiology, Colorado State University, Fort Collins, CO, USA.
PMID: 36346622 DOI: 10.1002/anie.202213563
Abstract

Increasing the speed, specificity, sensitivity, and accessibility of mycobacteria detection tools are important challenges for tuberculosis (TB) research and diagnosis. In this regard, previously reported fluorogenic trehalose analogues have shown potential, but their green-emitting dyes may limit sensitivity and applications in complex settings. Here, we describe a trehalose-based fluorogenic probe featuring a molecular rotor turn-on fluorophore with bright far-red emission (RMR-Tre). RMR-Tre, which exploits the unique biosynthetic Enzymes and environment of the mycobacterial outer membrane to achieve fluorescence activation, enables fast, no-wash, low-background fluorescence detection of live mycobacteria. Aided by the red-shifted molecular rotor fluorophore, RMR-Tre exhibited up to a 100-fold enhancement in M. tuberculosis labeling compared to existing fluorogenic trehalose probes. We show that RMR-Tre reports on M. tuberculosis drug resistance in a facile assay, demonstrating its potential as a TB diagnostic tool.

Keywords

Fluorescence; Molecular Rotor; Mycobacteria; Trehalose; Tuberculosis.

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