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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 inM. tuberculosislabeling compared to existing fluorogenic trehalose probes. We show that RMR‐Tre reports onM. tuberculosisdrug resistance in a facile assay, demonstrating its potential as a TB diagnostic tool.
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Indole‐3‐Glycerol Phosphate Synthase From Mycobacterium tuberculosis : A Potential New Drug Target
Abstract Tuberculosis (TB), caused by the pathogenMycobacterium tuberculosis, affects millions of people worldwide. Several TB drugs have lost efficacy due to emerging drug resistance and new anti‐TB targets are needed. Recent research suggests that indole‐3‐glycerol phosphate synthase (IGPS) inM. tuberculosis(MtIGPS) could be such a target. IGPS is a (β/α)8‐barrel enzyme that catalyzes the conversion of 1‐(o‐carboxyphenylamino)‐1‐deoxyribulose 5’‐phosphate (CdRP) into indole‐glycerol‐phosphate (IGP) in the bacterial tryptophan biosynthetic pathway.M. tuberculosisover expresses the tryptophan pathway genes during an immune response and inhibition ofMtIGPS allows CD4 T‐cells to more effectively fight againstM. tuberculosis. Here we review the published data onMtIGPS expression, kinetics, mechanism, and inhibition. We also discussMtIGPS crystal structures and compare them to other IGPS structures to reveal potential structure‐function relationships of interest for the purposes of drug design and biocatalyst engineering.
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- Award ID(s):
- 2030879
- PAR ID:
- 10303564
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ChemBioChem
- Volume:
- 23
- Issue:
- 2
- ISSN:
- 1439-4227
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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