Read our COVID-19 research and news.

Venomous. Strep A bacteria (above) is more likely to cause organ failure if the patient has a genetic variant.

Organ Failure Deciphered

Many patients who get life-threatening strep A infections share a gene that sends their immune system into overdrive when it encounters the bacteria, researchers report. The work could help explain why strep A is life-threatening for some while barely affecting others.

Group A streptococcus normally colonizes the skin and throat, causing strep throat and skin infections. But occasionally, the bug invades muscles and blood, sometimes leading to organ failure. Puzzlingly, the strain of group A strep implicated in the organ failure cases is no different than the bacteria isolated from patients with less life-threatening infections. Something about the patient, scientists believed, had to be affecting the outcome.

A multi-institutional team of researchers and clinicians, led by molecular biologist Malak Kotb at the University of Tennessee in Memphis, zeroed in on the part of the human genome that encodes surface receptors of immune cells, called antigen-presenting cells. When a foreign particle--such as a bacteria-produced toxin--binds to these receptors, the immune cell is activated and triggers fights against other invaders that share the same signature.

Kotb and her colleagues compared the DNA of 44 people who suffered organ failure from strep A infection, 108 people who suffered invasive strep infection but not organ failure, and 256 healthy volunteers. They found that those in the sickest group often shared a variant of a gene that produces the immune cell components that recognize bacterial toxins. Twenty-one percent of those in the organ failure group had the variant, compared to 1% in the other strep group and 5% in the healthy population, the researchers report in the 18 November online edition of Nature Medicine.

The researchers suggest that variant encodes a receptor that overreacts dramatically to the toxins, causing an inflammatory response. These receptors could predispose people to serious trouble: Instead of mobilizing a handful of defenders that can effectively fight the disease, the toxins bind to the antigen-presenting cells and activate about half of the T cell force, which then attack the body.

The work helps explain what causes the "giant spectrum of potential outcomes" in strep A infections, says molecular pathologist Victor Nizet of the University of California, San Diego. If tests are done for the gene, patients at greater risk for multiple organ failure can be identified early in the course of the infection.

Related sites
CDC Web page on strep A
Mount Sinai Group in Ontario