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

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 serovars to different species and tissues. We have recently shown that FimH adhesins from host-adapted serovars, e.g., Choleraesuis (Ch), bind to other glycoprotein receptors compared to FimH from host-unrestricted Enteritidis (E). Here we identify porcine calreticulin expressed by swine intestinal cells as a host-specific receptor for Ch FimH adhesin, suggesting that such an interaction may contribute to Ch host specificity. Calreticulin was identified by 2D electrophoresis and mass spectrometry as a glycoprotein that was bound specifically by recombinant Ch FimH protein, but not by FimH from E. The functionality of calreticulin as a specific receptor of Ch FimH adhesin was further confirmed by adhesion and invasion of mutated strains of Ch carrying different variants of FimH proteins to IPEC-J2 cells with overexpression and silenced expression of calreticulin. It was found that 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 E variant of FimH. Moreover, binding of Ch carrying the active variant of FimH to IPEC-J2 with silenced calreticulin expression was significantly weaker. Furthermore, we observed that Ch infection induces translocation of calreticulin to cell membrane. All of the aforementioned results lead to the general conclusion that host specificity requires not only special mechanisms and proteins expressed by the pathogen but also specifically recognized receptors expressed by a specific host.