E-037. Interference of Salmonella Motility and Type-Three Secretion by a Protective Anti-Lipopolysaccharide Monoclonal IgA Antibody

S. J. Forbes1,2, M. Eschmann1,2, T. Bumpus1, W. A. Samsonoff1, N. J. Mantis1,2;
1Wadsworth Ctr., New York State Dept. of Hlth., Albany, NY, 2Univ. at Albany, Albany, NY.

Secretory IgA (SIgA) antibodies directed against the serotype-specific, O-antigen of lipopolysaccharide (LPS) are the primary determinants of mucosal immunity to enteric bacterial pathogens, including Salmonella enterica serovar Typhimurium (S.Typhimurium). While the singular importance of SIgA in preventing enteric infections has been recognized for years, the underlying mechanisms by which this occurs are largely unknown. In this study, we present evidence that Sal4, a serotype-specific, anti-LPS monoclonal IgA antibody previously shown to be sufficient to protect mice against oral challenge with S.Typhimurium, is a potent inhibitor of bacterial motility and type-3 secretion, two processes necessary for adherence and invasion of intestinal epithelial cells. Sal4’s inhibitory effects occurred rapidly (<15 min), and were independent of the antibody’s ability to promote bacterial agglutination. Furthermore, SEM analysis revealed that Sal4-treatment caused dramatic alterations in the surface topology of S.Typhimurium, suggesting that inhibition of motility and type-3 secretion are the consequence of physical and/or mechanical stress on the LPS layer. These data may explain why Sal4 is so effective at preventing adherence and invasion of epithelial cells by S.Typhimurium in vitro and in vivo, and reveal a previously unrecognized capacity of SIgA to potentially “disarm” enteric pathogens on mucosal surfaces.