The researchers hypothesised that other bacteria might interact with CFTR in a similar manner. Finding no other lung pathogens that use the CFTR entry pathway, Dr. Pier and his colleagues turned their attention to the gastrointestinal tract, since its tissues also are affected directly in people with cystic fibrosis. Dr. Pier and his colleagues showed that normal CFTR protein also acts as a receptor for Salmonella typhi , the gastrointestinal pathogen that causes typhoid fever. The researchers then added to the cells antibodies and synthetic 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 the protruding CFTR segment as the S. typhi binding site through which it enters cells.
Epithelial cells ingest the bacterium, then slough off of the epithelial surface.
New epithelial cells soon take 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, any excess S. typhi are free to attack the underlying tissue, which lacks this defence mechanism. Since abnormal CFTR binds poorly to S. typhi, cystic fibrosis gene carriers would be protected from this infectious process and thus spared the high mortality associated with typhoid fever.