A Far-Red Fluorescent DNA Binder for Interaction Studies of Live Multidrug-Resistant Pathogens and Host Cells

Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11564-11568. doi: 10.1002/anie.201804090. Epub 2018 Aug 6.


Transgene expression of green fluorescent protein (GFP) has facilitated the spatiotemporal investigation of host-pathogen interactions; however, introduction of the GFP gene remains challenging in drug-resistant bacteria. Herein, we report a novel far-red fluorescent nucleic acid stain, 6-TramTO-3, which efficiently labels bacteria through a DNA binding mode without affecting growth and viability. Exemplarily, we stained Klebsiella pneumoniae, a major threat to hospitalized patients, and deciphered divergent interaction strategies of antibiotic-resistant and antibiotic-sensitive Klebsiella strains with immune cells. 6-TramTO-3 constitutes an off-the-shelf reagent for real-time analysis of bacterial infection, including strains for which the use of genetically encoded reporters is not feasible. Eventually, our approach may aid the development of strategies to combat a major worldwide health threat: multidrug-resistant bacteria.

Keywords: DNA recognition; antibiotics; far-red cyanine dyes; fluorescence-activated cell sorting; multidrug-resistant bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbocyanines / analysis*
  • DNA, Bacterial / analysis*
  • Drug Resistance, Multiple, Bacterial
  • Fluorescent Dyes / analysis*
  • Humans
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / cytology*
  • Klebsiella pneumoniae / isolation & purification
  • Macrophages / microbiology
  • Spectrometry, Fluorescence
  • Staining and Labeling


  • Carbocyanines
  • DNA, Bacterial
  • Fluorescent Dyes