A Nitrooxidoreductase Rv2466c-dependent Fluorescent Probe for Rapid Mycobacterium Tuberculosis Diagnosis and Drug Susceptibility Testing.

This study firstly demonstrated that natural product-inspired coumarin-based nitrofuranylcalanolides (NFCs) can form Rv2466c-mycothiol (MSH)-NFC (RvMN) ternary complex via NFC binding to W21, N51 and Y61 of Rv2466c and be spe-cifically reduced by Rv2466c, which is accompanied with the generation of high level of fluorescence. Additionally, the re-sults unveiled that the acetylated cysteine-glucosamine motif (AcCys-GlcN) of MSH is sufficient to interact with Rv2466c and adopt the active conformation that is essential for fully reducing NFCs. Further clinical translational investigation in this article indicated that the novel fluorescent NFC probe can serve as a much needed high-throughput and low-cost detection method for rapid detection of living Mtb and precise determination of MIC values of a full range of available drugs. This method can greatly facilitate the development of phenotypic drug-susceptibility testing (pDST) that will allow the point-of-care of treatment of TB within a week after diagnosis.