Scientists marvel at their new discovery.  The gene mutation responsible for cystic fibrosis also seems to protect against infection with typhoid fever bacteria as studied using fluorescent microscopy.  The finding might be the reason why approximately 12 million people in the United States carry the gene for such a highly fatal childhood disease.
Researchers led by Gerald Pier, Ph.D are enthusiastic about this findings inasmuch as it underscores how basic research in one disease area leads to discoveries in another area.  It is likewise a good sample of how pathogenesis   research creates opportunities for applied research.
More or less 2,500 babies are born with cystic fibrosis each year in the United States. Statistics indicate that before   1950s, most children afflicted with the disease died by age 1 or 2. Today, with new technology like fluorescent microscopy to study the disease, the average survival rate of these individuals is approximately 30 years.
Scientists have hypothesized that cystic fibrosis carriers likewise have enhanced protection against an infectious agent.  However, they did not have any idea which one. As examined through fluorescent microscopy, cystic fibrosis develops in children who inherit two mutant copies, one from each parent, of the gene responsible for the encoding of a protein known as cystic fibrosis transmembrane conductance regulator or CFTR.  As carefully studied in fluorescent microscopy an abnormal CFTR prevents the movement of chloride ions and water in the lungs, gastrointestinal tract, as well as in other tissues and causes them to secrete large amounts of mucus. Accumulated mucus in the lungs causes these children to become very susceptible to life-threatening respiratory infections.
One classic example for cystic firosis is the Pseudomonas aeruginosa since it manifests the primary clinical features of cystic fibrosis as viewed through fluorescent microscopy.  Dr. Pier and his colleagues reported that the normal CFTR protein acts as a receptor for P. aeruginosa as observed through fluorescent microscopy. It also helps clear this bacterium from the lung. It should be noted that when CFTR protein is abnormal or missing, it does not bind and ingest this bacterium. Lifelong infections are established in many individuals with cystic fibrosis.
The researchers theorized that other bacteria might likewise interact with CFTR in the same manner. Since Dr. Pier and company found no other lung pathogens that utilize the CFTR entry pathway, they focused their attention to the gastrointestinal tract, because its tissues also are affected directly in people with cystic fibrosis.
The normal CFTR protein also acts as a receptor for Salmonella typhi as observed through the use of fluorescent microscopy.  S. typhi is a gastrointestinal pathogen responsible for typhoid fever. How this pathogen looks could be viewed well using fluorescent microscopy. In tissue culture experiments examined with fluorescent microscopy they found that human cells expressing normal CFTR took up significantly more S. typhi as compared to other cells expressing mutant CFTR.  What the researchers then did was to add 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 hindered the uptake of S. typhi by CFTR, thereby identifying the protruding CFTR segment as the S. typhi binding site through which it enters cells.
The ingestion of S. typhi by epithelial cells is a function t of the body’s normal protective response. Epithelial cells ingest the bacterium, and then slough off the epithelial surface. Later, new epithelial cells soon take their place. As observed using fluorescent microscopy, at low concentrations of S. typhi, this process prevents infection. On the other hand, high concentrations can overpower this protective response.
The abnormal CFTR binds weakly to S. typhi.  As noted through fluorescent microscopy, cystic fibrosis gene carriers would be protected from this infectious process and therefore spared from the high mortality linked with typhoid fever.  Prior to 1900, typhoid fever was considered as a major infectious disease in the United States responsible for the death of about 15 percent of infected individuals. Typhoid fever still continues to remain as a grace problem in countries that lack adequate sewage treatment facilities.     Contaminated water is the major culprit of S. typhi transmission.
The findings could have important applications in the vaccine research especially in the efforts to develop S. typhi-based vaccine delivery vehicles.