Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France
Emile Auria
Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Patrick England
Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Plateforme de Biophysique Moléculaire, Paris, France
Julien Deschamps
Institut Micalis, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France
Romain Briandet
Institut Micalis, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France
Vanessa Kremer
Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France
Bruno Iannascoli
Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France
Léo Vidal-Maison
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France
Chunguang Guo
Regeneron Pharmaceuticals, Tarrytown, NY, USA
Lynn Macdonald
Regeneron Pharmaceuticals, Tarrytown, NY, USA
Séverine Péchiné
Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Orsay, France
Cécile Denève-Larrazet
Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Orsay, France
Bruno Dupuy
Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Guy Gorochov
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France
Pierre Bruhns
Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France
Delphine Sterlin
Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France
ABSTRACTClostridioides 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.