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

• Published in: Angewandte Chemie International Edition Vol. 62; no. 2; pp. e202213563 - n/a
• Main Authors: Banahene, Nicholas, Gepford, Dana M., Biegas, Kyle J., Swanson, Daniel H., Hsu, Yen‐Pang, Murphy, Brennan A., Taylor, Zachary E., Lepori, Irene, Siegrist, M. Sloan, Obregón‐Henao, Andrés, Van Nieuwenhze, Michael S., Swarts, Benjamin M.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 09.01.2023; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Chemistry; Chemistry, Multidisciplinary; Drug resistance; Fluorescence; Fluorescent Dyes; Humans; Molecular Probes; Molecular Rotor; Mycobacteria; Mycobacterium tuberculosis; Physical Sciences; Rotors; Science & Technology; Sensitivity; Trehalose; Tuberculosis; Tuberculosis; Trehalose; ANALOGS; Mycobacteria; Fluorescence; Molecular Rotor; MICROSCOPY
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202213563

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. The development of a novel trehalose‐based fluorogenic probe that features a molecular rotor turn‐on fluorophore with exceptionally bright far‐red emission is described (RMR‐Tre). RMR‐Tre enables rapid, no‐wash, low‐background fluorescence detection and drug‐susceptibility evaluation of live mycobacteria, including Mycobacterium tuberculosis.