Is Salmonella Typhi an Endotoxin?

Salmonella enterica serotype typhi, more commonly known as S. typhi, is the bacterium responsible for typhoid fever, a disease that causes an estimated 216,000 deaths annually, virtually all of which occur in developing countries, according to the World Health Organization. In patients treated with antibiotics, typhoid fever is seldom fatal; in patients left untreated, however, the mortality rate can be as high as 20 percent. A type of toxin called an endotoxin is partly responsible for the bacterium's virulence.

Endotoxins

• Some pathogenic or disease-causing bacteria secrete toxins that cause illness; others like Salmonella typhi release toxins after they die as their cell walls disintegrate. The latter kind of toxin is called an endotoxin. Endotoxins are a kind of molecule called a lipopolysaccharide, a lipid or fat molecule joined to a long chain of sugars. Ordinarily the endotoxin forms part of the cell wall; following the bacterium's demise, it's released to wreak havoc on the unfortunate host.

Salmonella typhi Toxin

• Like other pathogenic bacteria in the genus Salmonella, S. typhi releases endotoxins that provoke a violent reaction from the immune system. Once ingested, any S. typhi bacteria that make it through the strongly acidic environment in your stomach can penetrate the mucosal lining of your intestines and are engulfed by white blood cells called macrophages. Rather than being destroyed by the macrophages, however, the S. typhi bacteria hitch a ride inside their captors into the lymph nodes where they multiply. As some bacteria die, they release endotoxins; both live bacteria and endotoxins from the lymph may end up in the bloodstream.

Mechanism of Action

• Like other Salmonella endotoxins, the S. typhi endotoxin triggers a chain of events that activates a receptor called the Toll-like receptor-4 (TLR4) that's embedded in the membrane of some white blood cells and certain other cells. The alerted white blood cells secrete cytokines, powerful signaling molecules that kick your immune system into high gear. As your body ramps up its response, you begin to experience symptoms like chills and high fever. If the battle between your immune system and the bacteria rages out of control, it can lead to a condition called septic shock which may be fatal.

Later Stages

• Once the S. typhi bacteria have invaded the bloodstream, they may spread into other areas of the body. S. typhi usually colonizes the gallbladder, from where bacteria can re-enter the gastrointestinal tract again. The endotoxins and bacteria circulating in the bloodstream provoke an immune reaction. Delirium, diarrhea and high fever are common as the disease progresses. In those patients who recover, typhoid fever typically lasts two to three weeks. Since the immune system learns to recognize the bacteria, however, a single case confers immunity for life, although some patients become carriers.

Carriers

• Up to 3 percent of those who contract typhoid fever and recover may become carriers; they show no symptoms and suffer no further illness but continue to carry the bacteria in their gall bladder. Both carriers and patients can shed the bacteria in their urine and feces and thereby transmit it to others. Proper hygiene and sanitation are the best methods to prevent transmission. In the early 20th century prior to the advent of antibiotics, however, the disease was feared to the extent that some carriers were forcibly isolated. A BBC program in 2008 reported that between 1907 and the 1950s, nearly 50 carriers of typhoid fever were locked up in the isolation ward of a mental hospital in Surrey, England. Some of these unfortunate people remained there for the remainder of their lives.