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

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.

Hydrogel‐Based Biosensors for Bacterial Infections

“…This fluorescent probefunctionalized hydrogel was used to metabolically visualize bacterial infection on injured tissue in mice (Figure 3a). [47] Figure 3. Colorimetric hydrogels for enzyme-mediated bacterial detection.…”

Morphology‐Dependent Aggregation‐Induced Emission of Janus Emulsion Surfactants

“…[4,5] The approach further provides the basis for realtime, dosimetric and multi-analyte sensing arrays, ensuring low cost and high sensitivity. Examples for the latter include the development of FRET-based small-molecule chemiluminescent probes, [6] identification of precise microbiological and biochemical constituents within widely employed enzyme-linked immu-nosorbent assays (ELISA), [7] as well as dyes that display a triggerinduced aggregation-induced emission (AIE) enhancement, [8,9] that is, a fluorescence intensification upon the formation of aggregates. Innovations in new functional stimuli-responsive fluorescent material platforms complement the development of microscopic imaging techniques and promise to expand the capabilities of present hardware in imaging, biosensing platforms, or data storage and processing, with the goal to drive down the cost and ensure broad implementation of these methods.…”

Multifunctional nanofibrous mats: toward antibacterial and anti-inflammatory applications, and visual bacterial diagnosis

“…19 In this endeavor, visual diagnostic moieties are employed, including fluorescent probes and dye molecules. [20][21][22] However, these molecules are prone to leakage in the absence of complex chemical reactions. In addition, they are usually simple diagnostic moieties without therapeutic function.…”