Anti-S-layer monoclonal antibodies impact <i>Clostridioides difficile</i> physiology - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Article Dans Une Revue Gut microbes Année : 2024

Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology

Résumé

Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.
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hal-04535966 , version 1 (07-04-2024)

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Lise Hunault, Emile Auria, Patrick England, Julien Deschamps, Romain Briandet, et al.. Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology. Gut microbes, 2024, 16 (1), pp.1-17. ⟨10.1080/19490976.2023.2301147⟩. ⟨hal-04535966⟩
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