The Novel Type 1 Fimbriae FimH Receptor Calreticulin Plays a Role in Salmonella Host Specificity

Abstract

It was suggested that minor differences in the structure of FimH are most likely associated with differences in its adhesion specificities and may determine the tropism of various <i>Salmonella</i> serovars to different species and tissues. We have recently shown that FimH adhesins from host-adapted serovars, e.g., <i>Salmonella</i> Choleraesuis (<i>S</i>Ch), bind to other glycoprotein receptors compared to FimH from host-unrestricted <i>Salmonella</i> Enteritidis (<i>S</i>E). Here we identify porcine calreticulin expressed by swine intestinal cells as a host-specific receptor for <i>S</i>Ch FimH adhesin, suggesting that such an interaction may contribute to <i>S</i>Ch host specificity. Calreticulin was identified by 2D electrophoresis and mass spectrometry as a glycoprotein that was bound specifically by recombinant <i>S</i>Ch FimH protein, but not by FimH from <i>S</i>E. The functionality of calreticulin as a specific receptor of <i>S</i>Ch FimH adhesin was further confirmed by adhesion and invasion of mutated strains of <i>S</i>Ch carrying different variants of FimH proteins to IPEC-J2 cells with overexpression and silenced expression of calreticulin. It was found that <i>S</i>Ch carrying the active variant of FimH adhered and invaded IPEC-J2 cells with calreticulin overexpression at significantly higher numbers than those of SCh expressing the non-active variant or <i>S</i>E variant of FimH. Moreover, binding of <i>S</i>Ch carrying the active variant of FimH to IPEC-J2 with silenced calreticulin expression was significantly weaker. Furthermore, we observed that <i>S</i>Ch infection induces translocation of calreticulin to cell membrane. All of the aforementioned results lead to the general conclusion that <i>Salmonella</i> host specificity requires not only special mechanisms and proteins expressed by the pathogen but also specifically recognized receptors expressed by a specific host.