Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology.

Autor: Hunault L; Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France.; Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France.; Collège doctoral, Sorbonne Université, Paris, France., Auria E; Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France., England P; Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Plateforme de Biophysique Moléculaire, Paris, France., Deschamps J; Institut Micalis, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Briandet R; Institut Micalis, Université Paris-Saclay, INRAE, AgroParisTech, Jouy-en-Josas, France., Kremer V; Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France.; Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, Inserm, Châtenay-Malabry, France., Iannascoli B; Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France., Vidal-Maison L; Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France., Guo C; Regeneron Pharmaceuticals, Tarrytown, NY, USA., Macdonald L; Regeneron Pharmaceuticals, Tarrytown, NY, USA., Péchiné S; Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Orsay, France., Denève-Larrazet C; Equipe Bactéries Pathogènes et Santé, Faculté de Pharmacie, Institut MICALIS (UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech), Orsay, France., Dupuy B; Laboratoire Pathogenèse des Bactéries Anaérobies, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France., Gorochov G; Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France., Bruhns P; Antibodies in Therapy and Pathology, Institut Pasteur, Université Paris-Cité, Inserm UMR1222, Paris, France., Sterlin D; Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Inserm, CNRS, Paris, France.
Jazyk: angličtina
Zdroj: Gut microbes [Gut Microbes] 2024 Jan-Dec; Vol. 16 (1), pp. 2301147. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1080/19490976.2023.2301147
Abstrakt: 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.
Databáze: MEDLINE
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