Molecular basis for the enterocyte tropism exhibited by Salmonella typhimurium type 1 fimbriae

Salmonella typhimurium exhibits a distinct tropism for mouse enterocytes th at is linked to their expression of type 1 fimbriae, The distinct binding t raits of Salmonella type 1 fimbriae is also reflected in their binding to s elected mannosylated proteins and in their ability to promote secondary bac terial aggregation on enterocyte surfaces. The determinant of binding in Sa lmonella type I fimbriae is a 35-kDa structurally distinct fimbrial subunit , FimHs, because inactivation of fimHs abolished binding activity in the re sulting mutant without any apparent effect on fimbrial expression. Surprisi ngly, when expressed in the absence of other fimbrial components and as a t ranslational fusion protein with MalE, FimHs failed to demonstrate any spec ific binding tropism and bound equally to all cells and mannosylated protei ns tested. To determine if the binding specificity of Salmonella type 1 fim briae was determined by the fimbrial shaft that is intimately associated wi th FimHs, we replaced the amino-terminal half of FimHs with the correspondi ng sequence from Escherichia coli FimH (FimHE) that contains the receptor b inding domain of FimHE, The resulting hybrid fimbriae bearing FimHES on a S almonella fimbrial shaft exhibited binding traits that resembled that of Sa lmonella rather than E, coli fimbriae, Apparently, the quaternary constrain ts imposed by the fimbrial shaft on the adhesin determine the distinct bind ing traits of S. typhimurium type 1 fimbriae.