The Type IVB Pili of Salmonella Enterica Serovar Typhi Bind to the Cystic Fibrosis Transmembrane Conductance Regulator

Salmonella enterica serovar Typhi expresses type IVB pili. We show that the prePilS protein (the soluble precursor form of the structural pilin) interacts with a 15-mer peptide representing the first extracellular domain of the cystic fibrosis transmembrane conductance regulator (CFTR), a recognized human epithelial cell receptor for serovar Typhi (G. B. Pier et al., Nature 393:79-82, 1998). This indicates that after mediating bacterial self-association (C. Morris et al., Infect. Immun. 71:1141-1146, 2003), the pili then act to attach the bacterial clumps to CFTR in the membrane of gut epithelial cells. These sequential type IVB pilus-mediated events cannot be performed by (for example) S. enterica serovar Typhimurium, which may explain why only serovar Typhi causes epidemics of enteric fever in humans.