A Far-Red Molecular Rotor Fluorogenic Trehalose Probe for Live Mycobacteria Detection and Drug-Susceptibility Testing
Nicholas Banahene
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
These authors contributed equally to this work.
Search for more papers by this authorDana M. Gepford
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
These authors contributed equally to this work.
Search for more papers by this authorKyle J. Biegas
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorDaniel H. Swanson
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorYen-Pang Hsu
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorBrennan A. Murphy
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorZachary E. Taylor
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorIrene Lepori
Department of Microbiology, University of Massachusetts, Amherst, MA, USA
Search for more papers by this authorProf. Dr. M. Sloan Siegrist
Department of Microbiology, University of Massachusetts, Amherst, MA, USA
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA
Search for more papers by this authorDr. Andrés Obregón-Henao
Department of Microbiology, Colorado State University, Fort Collins, CO, USA
Search for more papers by this authorProf. Dr. Michael S. Van Nieuwenhze
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Benjamin M. Swarts
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorNicholas Banahene
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
These authors contributed equally to this work.
Search for more papers by this authorDana M. Gepford
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
These authors contributed equally to this work.
Search for more papers by this authorKyle J. Biegas
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorDaniel H. Swanson
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorYen-Pang Hsu
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorBrennan A. Murphy
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorZachary E. Taylor
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorIrene Lepori
Department of Microbiology, University of Massachusetts, Amherst, MA, USA
Search for more papers by this authorProf. Dr. M. Sloan Siegrist
Department of Microbiology, University of Massachusetts, Amherst, MA, USA
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA
Search for more papers by this authorDr. Andrés Obregón-Henao
Department of Microbiology, Colorado State University, Fort Collins, CO, USA
Search for more papers by this authorProf. Dr. Michael S. Van Nieuwenhze
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA
Department of Chemistry, Indiana University, Bloomington, IN, USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Benjamin M. Swarts
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA
Biochemistry, Cellular, and Molecular Biology Program, Central Michigan University, Mount Pleasant, MI, USA
Search for more papers by this authorAbstract
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.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
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