Toward Point-of-Care Detection of Mycobacterium tuberculosis : A Brighter Solvatochromic Probe Detects Mycobacteria within Minutes.

There is an urgent need for point-of-care tuberculosis (TB) diagnostic methods that are fast, inexpensive, and operationally simple. Here, we report on a bright solvatochromic dye trehalose conjugate that specifically detects Mycobacterium tuberculosis (Mtb) in minutes. 3-Hydroxychromone (3HC) dyes, known for having high fluorescence quantum yields, exhibit shifts in fluorescence intensity in response to changes in environmental polarity. We synthesized two analogs of 3HC-trehalose conjugates (3HC-2-Tre and 3HC-3-Tre) and determined that 3HC-3-Tre has exceptionally favorable properties for Mtb detection. 3HC-3-Tre-labeled mycobacterial cells displayed a 10-fold increase in fluorescence intensity compared to our previous reports on the dye 4,4- N,N -dimethylaminonapthalimide (DMN-Tre). Excitingly, we detected fluorescent Mtb cells within 10 min of probe treatment. Thus, 3HC-3-Tre permits rapid visualization of mycobacteria that ultimately could empower improved Mtb detection at the point-of-care in low-resource settings.
Competing Interests: The authors declare the following competing financial interest(s): M.K. and C.R.B. are cofounders of OliLux Biosciences which has licensed patents related to the work in this paper. B.K. is a scientific advisor to OliLux Biosciences. B.K is cofounder of SmartSpot Quality CC and scientific advisor to SmartSpot Quality CC and Pulmosat. C.R.B. is a cofounder and scientific advisory board member of Lycia Therapeutics, Palleon Pharmaceuticals, Enable Bioscience, Redwood Biosciences (a subsidiary of Catalent), and InterVenn Biosciences, and a member of the board of directors of Eli Lilly & Company.
(© 2021 The Authors. Published by American Chemical Society.)