Mucosal Antibodies to the C Terminus of Toxin A Prevent Colonization of Clostridium difficile

Abstract

Mucosal immunity is considered important for protection against <i>Clostridium difficile</i> infection (CDI). We show that in hamsters immunized with <i>Bacillus subtilis</i> spores expressing a carboxy-terminal segment (TcdA_26-39) of <i>C. difficile</i> toxin A, no colonization occurs in protected animals when challenged with <i>C. difficile</i> strain 630. In contrast, animals immunized with toxoids showed no protection and remained fully colonized. Along with neutralizing toxins, antibodies to TcdA_26-39 (but not to toxoids), whether raised to the recombinant protein or to TcdA_26-39 expressed on the <i>B. subtilis</i> spore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat of <i>C. difficile</i> These include two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA_26-39 mucosal antibodies obtained following immunization with recombinant <i>B. subtilis</i> spores were able to reduce the adhesion of <i>C. difficile</i> to mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection against CDI.