Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues

Chen Jian Zhong, Xi Le Hu, Xiao Lan Yang, Hui Qi Gan, Kai Cheng Yan, Fu Ting Shu, Pei Wei, Teng Gong, Peng Fei Luo, Tony D. James, Zhao Hong Chen, Yong Jun Zheng, Xiao Peng He, Zhao Fan Xia

Research output: Contribution to journalArticlepeer-review

1 Citation (SciVal)

Abstract

The ability to effectively detect bacterial infection in human tissues is important for the timely treatment of the infection. However, traditional techniques fail to visualize bacterial species adhered to host cells in situ in a target-specific manner. Dihydropteroate synthase (DHPS) exclusively exists in bacterial species and metabolically converts p-aminobenzoic acid (PABA) to folic acid (FA). By targeting this bacterium-specific metabolism, we have developed a fluorescent imaging probe, PABA-DCM, based on the conjugation of PABA with a long-wavelength fluorophore, dicyanomethylene 4H-pyran (DCM). We confirmed that the probe can be used in the synthetic pathway of a broad spectrum of Gram-positive and negative bacteria, resulting in a significantly extended retention time in bacterial over mammalian cells. We validated that DHPS catalytically introduces a dihydropteridine group to the amino end of the PABA motif of PABA-DCM, and the resulting adduct leads to an increase in the FA levels of bacteria. We also constructed a hydrogel dressing containing PABA-DCM and graphene oxide (GO), termed PABA-DCM@GO, that achieves target-specific fluorescence visualization of bacterial infection on the wounded tissues of mice. Our research paves the way for the development of fluorescent imaging agents that target species-conserved metabolic pathways of microorganisms for the in situ monitoring of infections in human tissues.

Original languageEnglish
Pages (from-to)39808-39818
Number of pages11
JournalACS Applied Materials and Interfaces
Volume14
Issue number35
Early online date25 Aug 2022
DOIs
Publication statusPublished - 7 Sep 2022

Keywords

  • bacteria
  • fluorescence imaging
  • folate
  • metabolism
  • wound infection

ASJC Scopus subject areas

  • Materials Science(all)

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