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Fast Broad-Spectrum Staining and Photodynamic Inhibition of Pathogenic Microorganisms by a Water-Soluble Aggregation-Induced Emission Photosensitizer

ABSTRACT: Pathogenic microorganisms pose great challenges to public health, which is constantly urgent to develop extra strategies for the fast staining and efficient treatments. In addition, once bacteria form stubborn biofilm, extracellular polymeric substance (EPS) within biofilm can act as protective barriers to prevent external damage and inward diffusion of traditional antibiotics, which makes it frequently develop drug-resistant ones and even hard to treat. Therefore, it is imperative to develop more efficient methods for the imaging/detection and efficient inhibition of pathogenic microorganisms. Here, a water-soluble aggregation-induced emission (AIE)-active photosensitizer TPA-PyOH was employed for fast imaging and photodynamic treatment of several typical pathogens, such as S. aureus, methicillin-resistant Staphylococcus aureus, L. monocytogenes, C. albicans, and E. coli. TPA-PyOH was non-fluorescent in water, upon incubation with pathogen, positively charged TPA-PyOH rapidly adhered to pathogenic membrane, thus the molecular motion of TPA-PyOH was restricted to exhibit AIE-active fluorescence for turn-on imaging with minimal background. Upon further white light irradiation, efficient reactive oxygen species (ROS) was in-situ generated to damage the membrane and inhibit the pathogen eventually. Furthermore, S. aureus biofilm could be suppressed in vitro. Thus, water-soluble TPA-PyOH was a potent AIE-active photosensitizer for fast fluorescent imaging with minimal background and photodynamic inhibition of pathogenic microorganisms.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC8593337 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:Detection of bacteria-specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l-arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose-derived 18 F analogs for their incorporation into pathogenic bacteria. PROCEDURES:We synthesized four radiolabeled arabinofuranose-derived sugars: 2-deoxy-2-[18 F]fluoro-arabinofuranoses (d-2-18 F-AF and l-2-18 F-AF) and 5-deoxy-5-[18 F]fluoro-arabinofuranoses (d-5-18 F-AF and l-5-18 F-AF). The arabinofuranoses were synthesized from 18 F- via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2-deoxy-2-[18 F]fluoro-d-glucose ([18 F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d-2-18 F-AF and l-2-18 F-AF to key human pathogens was investigated in vitro. RESULTS:All 18 F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d-2-18 F-AF and l-2-18 F-AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d-2-18 F-AF and l-2-18 F-AF demonstrated sensitivity to most gram-positive and gram-negative bacteria. CONCLUSIONS:Arabinofuranose-derived 18 F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5-substitued analogs, a finding that may have mechanistic implications for related tracers. Both d-2-18 F-AF and l-2-18 F-AF showed sensitivity to most gram-negative and gram-positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection.

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Fast Broad-Spectrum Staining and Photodynamic Inhibition of Pathogenic Microorganisms by a Water-Soluble Aggregation-Induced Emission Photosensitizer

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