A new study identifies a single molecule as a key entry point for two dangerous bacteria to break through cell barriers and cause disease. The findings, published March 19 in the journal mBio, suggest that blocking the interaction between molecules (called CD40) and bacteria may be a common strategy to prevent life-threatening diseases, including toxic shock syndrome.

Staphylococcus aureus (Staphylococcus) and Streptococcus pyogenes can cause many serious diseases. According to the Centers for Disease Control and Prevention, staphylococci cause 70000 cases of highly fatal pneumonia each year, 40000 cases of severe heart infection and more than 500000 cases of postoperative infection. Streptococcus pyogenes causes 10 million cases of sore throat and 30000 cases of severe invasive diseases each year.

“many of the infections caused by these two bacteria begin on the surface of the skin or mucous membrane, such as the nasal cavity, oral cavity, throat, intestine and vagina. The ability of these bacteria to cause disease depends on the production of a family of toxins called superantigens, which can lead to particularly harmful inflammation.” Explained Dr. Patrick Schlievert, professor of microbiology and immunology at the University of Iowa, Carver College of Medicine and lead author of the new study.

Previous studies by Schlievert have shown that superantigens cause epithelial cells in the mucosal barrier to produce signaling molecules called chemokines. These chemokines attract immune cells, destroy the integrity of the mucosal barrier, allow superantigens and bacteria themselves to penetrate and lead to serious and often fatal diseases, including toxic shock syndrome.

In the new study, Schlievert and his colleagues in UI and National Jewish Health, New York, used human vaginal epithelial cells as a model for mucosal barriers. They suggest that the interaction between CD40 and superantigens triggers the production of chemokines in these cells. Using CRISPR gene editing to remove CD40 from cells can prevent the production of chemokine induced by bacterial superantigen. In contrast, those cells that reduced the CD40 gene restored the ability to produce chemokines triggered by superantigens.

The team tested three superantigens: toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxins B and staphylococcal enterotoxins C. Of the three, TSST-1 has the strongest effect, which may explain why this superantigen is responsible for all menstrual toxicity and shock syndrome.

“CD40 is crucial; without it, you wouldn’t react to superantigens,” Schlievert said. “since we now know that the two bacterial families cause disease through the same human tissue receptors, we are looking for ways to block the interaction between CD40 and superantigens to prevent immune activation. This work also offers many possibilities to prevent other pathogens, that is, to treat related diseases by preventing the interaction of the same receptors with pathogens. These studies are under way.

“if the central pathway used by many pathogens to break down the mucosal barrier is the same, it means that we only need to target one target to prevent the pathogen from destroying the barrier. This could be a huge possibility for the prevention and treatment of pathogens.” he added.