Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology

Hunault, L.; Auria, E.; England, P.; Deschamps, J.; Briandet, R.; Kremer, V.; Iannascoli, B.; Vidal-Maison, L.; Guo, C.; Macdonald, L.; Pechine, S.; Deneve-Larrazet, C.; Dupuy, B.; Gorochov, G.; Bruhns, P.; Sterlin, D.

doi:10.1101/2023.09.21.558785

bioRxiv · 10.1101/2023.09.21.558785

Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology

Hunault, L.·Auria, E.·England, P.·Deschamps, J.·Briandet, R.·Kremer, V.·Iannascoli, B.·Vidal-Maison, L.·Guo, C.·Macdonald, L.·Pechine, S.·Deneve-Larrazet, C.·Dupuy, B.·Gorochov, G.·Bruhns, P.·Sterlin, D.

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Abstract

Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults and is characterized by high levels of recurrence and mortality. Surface-layer Protein A (SlpA), the most expressed protein on bacterial surface, plays a crucial role in the early stages of infection although its role in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and correlate with improved outcome of C. difficile infection (CDI). However, the precise mechanisms of how anti-S-layer antibodies can confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting S-layer of the reference strain 630. Characterization of these mAbs unravels important roles for S-layer protein in growth, toxin secretion, and biofilm formation with, surprisingly, opposite effects of different anti-SlpA mAbs on these functions. One anti-SlpA mAb impaired C. difficile growth and restored sensitivity to lysozyme-induced lysis. These findings suggest that anti-S-layer antibody responses may include protective and detrimental effects for the host and provide important insights for designing adequate S-layer-targeting therapeutics.

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Hunault, L., Auria, E., England, P., Deschamps, J., Briandet, R., Kremer, V., Iannascoli, B., Vidal-Maison, L., Guo, C., Macdonald, L., Pechine, S., Deneve-Larrazet, C., Dupuy, B., Gorochov, G., Bruhns, P., Sterlin, D.. 2023-09-21. Anti-S-layer monoclonal antibodies impact Clostridioides difficile physiology. https://doi.org/10.1101/2023.09.21.558785

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