Combating Pathogenic Immune Evasion: Sialidase-Activated Thermally Delayed Fluorescence for Probing and Modulating...

Area of Science:

• Microbiology
• Immunology
• Biochemistry

Background:

• Innate immunity relies on phagocytosis, but pathogens like Clostridium perfringens evade this defense.
• Bacterial immune evasion strategies, particularly those targeting host defense mechanisms, require further investigation.
• Sialidase, a C. perfringens virulence factor, is crucial for immune evasion and presents a potential therapeutic target.

Purpose of the Study:

• To develop a sensitive and selective molecular tool for detecting C. perfringens sialidase activity.
• To utilize this tool for screening potential sialidase inhibitors.
• To evaluate the therapeutic potential of identified inhibitors in combating C. perfringens immune evasion.

Main Methods:

• Development of a "turn-on" thermally activated delayed fluorescent probe (SA-HBT-PXZ) for sialidase sensing.
• Time-resolved fluorescence imaging of C. perfringens in various biological samples (live cells, tissues, infected mice).
• High-throughput screening of sialidase inhibitors using prompt and delayed fluorescence emissions.

Main Results:

• The SA-HBT-PXZ probe demonstrated high selectivity and sensitivity for detecting C. perfringens sialidase.
• Successful imaging of C. perfringens in complex biological environments was achieved.
• Screening identified lead compounds that inhibit sialidase activity, promoting M1 macrophage differentiation and enhancing bacterial phagocytosis.

Conclusions:

• The developed fluorescent probe SA-HBT-PXZ is a valuable tool for studying C. perfringens sialidase.
• Inhibiting C. perfringens sialidase can restore host immune defense mechanisms, specifically macrophage phagocytosis.
• This research offers promising therapeutic targets and lead compounds for treating C. perfringens infections.