Insights into IrtAB: Iron Transport Facilitates Ultrasensitive Detection of Mycobacteria in Both Cellular and Clinical Environments

  • ACS Cent Sci. 2025 Jan 7;11(2):261-271. doi: 10.1021/acscentsci.4c00676.
Dianmo Ni  1 ,  Xiaoqiao Hong  1 ,  Dingyi Liu  2  3 ,  Xueyuan Li  1 ,  Li Li  4 ,  Wenwu Liu  1 ,  Zhaogang Sun  2  3 ,  Gang Liu  1
Affiliations
  • 1. School of Pharmaceutical Sciences, Tsinghua University, Haidian District, Beijing 100084, P. R. China.
  • 2. Translational Medicine Center, Beijing Chest Hospital, Capital Medical University, Tongzhou District, Beijing 101149, P. R. China.
  • 3. Beijing Key Laboratory in Drug Resistant Tuberculosis Research, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing 101149, P. R. China.
  • 4. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Xicheng District, Beijing 100050, P. R. China.
PMID: 40028350 DOI: 10.1021/acscentsci.4c00676
Abstract

Mycobacterium tuberculosis (Mtb) utilizes a heterodimeric ABC transporter (IrtAB) to extract Fe3+ ions from host cells. This study demonstrates that ultrasensitive fluorescent probes, achieved through the conjugation of fluorophores with the ligand of IrtAB, N14G and N14G-Fe can detect Mycobacterium smegmatis at concentrations as low as 1-10 nM within an incubation period of less than 5 min. Furthermore, these probes effectively label Mycobacterium bovis Bacille Calmette-Guérin BCG and the wild-type Mtb strain H37Rv at a concentration of 0.1 μM after 10 min of incubation, achieving a limit of detection of 34 Colony-Forming Unit for the wild-type Mtb strain H37Rv. Both N14G and N14G-Fe successfully identified Mtb in sputum samples from patients diagnosed with tuberculosis, exhibiting exceptional fluorescence.

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