Salmonella typhi uses CFTR to enter intestinal epithelial cells

Gerald B. Pier (), Martha Grout, Tanweer Zaidi, Gloria Meluleni, Simone S. Mueschenborn, George Banting, Rosemary Ratcliff, Martin J. Evans and William H. Colledge
Additional contact information
Gerald B. Pier: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School
Martha Grout: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School
Tanweer Zaidi: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School
Gloria Meluleni: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School
Simone S. Mueschenborn: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School
George Banting: Molecular Recognition Centre, University of Bristol
Rosemary Ratcliff: University of Cambridge
Martin J. Evans: Tennis Court Road, University of Cambridge
William H. Colledge: University of Cambridge

Nature, 1998, vol. 393, issue 6680, 79-82

Abstract: Abstract Homozygous mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF). In the heterozygous state, increased resistance to infectious diseases may maintain mutant CFTR alleles at high levels in selected populations1. Here we investigate whether typhoid fever could be one such disease. The disease is initiated when Salmonella typhi enters gastrointestinal epithelial cells for submucosal translocation2. We found that S. typhi, but not the related murine pathogen S. typhimurium, uses CFTR for entry into epithelial cells. Cells expressing wild-type CFTR internalized more S. typhi than isogenic cells expressing the most common CFTR mutation, a phenylalanine deleted at residue 508 (Δ508). Monoclonal antibodies and synthetic peptides containing a sequence corresponding to the first predicted extracellular domain of CFTR inhibited uptake of S. typhi. Heterozygous ΔF508 Cftr mice translocated 86% fewer S. typhi into the gastrointestinal submucosa than wild-type Cftr mice; no translocation occurred in ΔF508 Cftr homozygous mice. The Cftr genotype had no effect on the translocation of S. typhimurium. Immunoelectron microscopy revealed that more CFTR bound to S. typhi in the submucosa of Cftr wild-type mice than in ΔF508 heterozygous mice. We conclude that diminished levels of CFTR in heterozygotes may decrease susceptibility to typhoid fever.

Date: 1998
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DOI: 10.1038/30006

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