Dr. Pier and his colleagues showed that normal CFTR protein also acts as areceptor for Salmonella typhi, the gastrointestinal pathogen that causes typhoidfever. The researchers then added to the cells antibodies andsynthetic molecules designed to bind to a segment of the CFTR molecule that protrudes from the cell membrane. These agents blocked the uptake of S. typhi by CFTR, thus identifying theprotruding CFTR segment as the S. typhi binding site through which it enterscells.
Epithelial cells ingest thebacterium, then slough off of the epithelial surface.
New epithelial cells soontake their place. At low concentrations of S. typhi, this process prevents infection. High concentrations, however, can overwhelm this protective response. After S.typhi-ingesting epithelial cells have been shed from the epithelial surface, anyexcess S. typhi are free to attack the underlying tissue, which lacks thisdefense mechanism. Since abnormal CFTR binds poorly to S. typhi, cystic fibrosis gene carrierswould be protected from this infectious process and thus spared the highmortality associated with typhoid fever.