From Bench to Clinic: A Nitroreductase Rv3368c-Responsive Cyanine-Based Probe for the Specific Detection of Live Mycobacterium tuberculosis

  • Anal Chem. 2024 Jan 30;96(4):1576-1586. doi: 10.1021/acs.analchem.3c04293.
Xiaoqiao Hong  1 ,  Pengfei Geng  1 ,  Na Tian  2 ,  Xueyuan Li  1 ,  Mengqiu Gao  2 ,  Lihui Nie  2 ,  Zhaogang Sun  2  3 ,  Gang Liu  1
Affiliations
  • 1. School of Pharmaceutical Sciences, Tsinghua University, Haidian District, Beijing 100084, China.
  • 2. Translational Medicine Center, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
  • 3. Beijing Key Laboratory in Drug Resistant Tuberculosis Research, Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, China.
PMID: 38190499 DOI: 10.1021/acs.analchem.3c04293
Abstract

Tuberculosis (TB), characterized by high mortality and low diagnosis, is caused by a single pathogen, Mycobacterium tuberculosis (Mtb). Imaging tools that can be used to track Mtb without pre-labeling and to diagnose live Mtb in clinical samples can shorten the gap between bench and clinic, fuel the development of novel anti-TB drugs, strengthen TB prevention, and improve patient treatment. In this study, we report an unprecedented novel nitroreductase-responsive cyanine-based fluorescent probe (Cy3-NO2-tre) that rapidly and specifically labels Mtb and detects it in clinical samples. Cy3-NO2-tre generated fluorescence after activation by a specific nitroreductase, Rv3368c, which is conserved in the Mycobacteriaceae. Cy3-NO2-tre effectively imaged mycobacteria within infected host cells, tracked the Infection process, and visualized Mycobacterium smegmatis being endocytosed by macrophages. Cy3-NO2-tre also detected Mtb in the sputum of patients with TB and exhibited excellent photostability. Furthermore, the Cy3-NO2-tre/auramine O percentage change within 7 ± 2 days post drug treatment in the sputum of inpatients was closely correlated with the reexamination results of the chest computed tomography, strongly demonstrating the clinical application of Cy3-NO2-tre as a prognostic indicator in monitoring the therapeutic efficacy of anti-TB drugs in the early patient care stage.

Products