Human umbilical cord MSC-derived exosomes potently inhibit *Clostridium perfringens* growth via Hsp70 binding

Clostridium perfringens is a common commensal and pathogen in the human and animal gastrointestinal tract, contributing to various infections. The increasing global challenge of antimicrobial resistance necessitates the exploration of novel therapeutic strategies beyond conventional antibiotics. Mesenchymal stem cells (MSCs) are known for their regenerative and immunomodulatory properties, largely mediated by their secreted exosomes. These nanosized vesicles, laden with bioactive molecules, offer a promising, cell-free alternative for addressing bacterial infections, potentially circumventing resistance mechanisms.

This study investigated the antibacterial potential of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) against Clostridium perfringens using both in vitro experimental methods and in silico molecular docking. The in vitro component assessed the direct anti-C. perfringens activity of the exosomes. For the in silico analysis, researchers performed molecular docking simulations to identify potential binding interactions between exosomal proteins and essential bacterial enzymes. Specifically, they focused on interactions with bacterial RNA polymerase and ATP synthase to elucidate the underlying mechanisms of action.

Human umbilical cord mesenchymal stem cell–derived exosomes (hUC-MSC-Exos) demonstrated potent anti-Clostridium perfringens activity in experimental in vitro assays. The in silico molecular docking analysis provided mechanistic insights, revealing strong binding affinities between specific exosomal proteins and critical bacterial enzymes. The 70 kDa heat shock protein (Hsp70), an abundant exosomal component, showed particularly robust interactions. > Hsp70 exhibited a strong binding affinity to bacterial ribonucleic acid (RNA) polymerase with a docking score of -1088.0, suggesting a potential disruption of bacterial transcription. Furthermore, Hsp70 also demonstrated significant binding to bacterial adenosine triphosphate (ATP) synthase, achieving a docking score of -1021.4, indicating interference with bacterial energy production. These findings collectively suggest that the antibacterial effects of hUC-MSC-Exos are likely mediated through the inhibition of essential bacterial enzymatic functions.