ANGIE 5: A NOVEL ANTIMICROBIAL PEPTIDE WITH POTENT INHIBITORY ACTIVITY AGAINST CLOSTRIDIOIDES DIFFICILE TOXINS

• Dr. Beatriz M. Ferreira

  Department of Microbiology and Immunology, University of Toronto, Canada

  Author

• Dr. Matteo R. Bianchi

  Faculty of Biology, University of Warsaw, Poland

  Author

Clostridioides difficile infection (CDI) remains a significant global health concern, primarily driven by the action of large clostridial toxins, TcdA and TcdB. These toxins are responsible for the severe gastrointestinal symptoms and systemic complications associated with CDI. Current therapeutic approaches face challenges, including the rise of antibiotic resistance and recurrent infections. This study investigates the potential of Angie 5, a novel antimicrobial peptide (AMP) derived from the angiogenin family, as a therapeutic agent against C. difficile toxins. Our findings demonstrate that Angie 5 effectively inhibits both TcdA- and TcdB-induced cytotoxicity in cellular models and delays intracellular Rac1 glucosylation. Furthermore, computational and biochemical analyses suggest a direct interaction between Angie 5 and the toxins, potentially interfering with their cellular uptake or subsequent intracellular processing, rather than direct in vitro enzymatic inhibition. These results highlight Angie 5 as a promising candidate for the development of novel anti-toxin strategies against CDI, offering a potential alternative or adjunct to conventional antibiotic treatments.

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