Salmonella enterica serovar typhi uses Type IVB pili to enter human intestinal epithelial cells via the human cystic fibrosis transmembrane conductance regulator

2000 ◽  
Author(s):  
Cecilia Ming Chi Yip
2002 ◽  
Vol 70 (11) ◽  
pp. 6416-6423 ◽  
Author(s):  
Jeffrey B. Lyczak ◽  
Gerald B. Pier

ABSTRACT The cystic fibrosis transmembrane conductance regulator (CFTR) protein is an epithelial receptor mediating the translocation of Salmonella enterica serovar Typhi to the gastric submucosa. Since the level of cell surface CFTR is directly related to the efficiency of serovar Typhi translocation, the goal of this study was to measure CFTR expression by the intestinal epithelium during infection. CFTR protein initially present in the epithelial cell cytoplasm was rapidly trafficked to the plasma membrane following exposure to live serovar Typhi or bacterial extracts. CFTR-dependent bacterial uptake by epithelial cells increased (>100-fold) following CFTR redistribution. The bacterial factor which triggers CFTR redistribution is heat and protease sensitive. These data suggest that serovar Typhi induces intestinal epithelial cells to increase membrane CFTR levels, leading to enhanced bacterial ingestion and submucosal translocation. This could be a key, early step in the infectious process leading to typhoid fever.


2003 ◽  
Vol 71 (10) ◽  
pp. 6049-6050 ◽  
Author(s):  
Inez S. M. Tsui ◽  
Cecilia M. C. Yip ◽  
Jim Hackett ◽  
Christina Morris

ABSTRACT 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.


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