Typhoid fever is a predominantly gastric bacterial disease that is found worldwide and is caused by the bacterium Salmonella entrerica serovar Typhi (S. Typhi). Typhoid is one of the most well documented diseases in history having ravaged populations as old as the Athenians of ancient Greece and as new as the citizens of Chicago less than a century ago. Modern sanitation and hygiene practices have all but eradicated the disease in developed nations but developing nations are still heavily impacted with over 200,000 deaths annually. S. Typhi is very closely related to the more well-known Salmonella strains that cause a usually non-fatal, if uncomfortable, case of gastroenteritis. Up until very recently it was not known why this strain, that is almost identical genetically, causes a systemic and life-threatening disease while its cousins did not.
Recent research by Yale scientists Jeongmin Song, Xiang Gao and Jorge Galan has suggested that A2B5 typhoid toxin is responsible for S. Typhi’s deadliness. This toxin is comprised of 3 subunits commonly found in less fatal toxins that, when put together, are far more dangerous than the individual parts. Once S. Typhi has infected a mammalian host cell it begins to produce A2B5 toxins which are secreted by the infected cell into the host where they causes DNA damage and encourages cell-cycle arrest. The researchers tested the toxin by introducing it into mice which proceeded to show a majority of the commonly seen symptoms of typhoid fever including lethargy, stupor, malaise, weight loss and eventual death. The toxin was also observed to intoxicate and damage a variety of epithelial cells (such as those lining the intestinal wall) and immune cells. This new knowledge promises the possibility of treatments. Vaccines and therapeutics that target toxins have historically proven to be very effective and successful.