University of Tübingen: Research team from Tübingen develops a new strategy against sepsis

Some blood poisoning is mild, but many are fatal – the reasons for these differences have remained in the dark despite decades of research. Researchers at the University of Tübingen have now discovered a possible cause and, on this basis, have developed a new experimental strategy to combat bacterial sepsis. The new therapeutic approach against life-threatening blood poisoning does not require the use of antibiotics and instead relies on stimulating the body’s own immune system by administering the active ingredient acetate. The study, published in the journal Communications Biology was published, scientists from the Cluster of Excellence “Control of Microorganisms to Fight Infections” (CMFI), the Interfaculty Institute for Microbiology and Infection Research at the University of Tübingen (IMIT) and the German Center for Infection Research (DZIF) were involved.

As a result of a local infection, bacteria can penetrate the bloodstream, which can lead to life-threatening sepsis (colloquially blood poisoning) and septic shock with organ failure. Methicillin-resistant Staphylococcus aureus bacteria (MRSA), which have developed resistance to many of the common antibiotics, are among the most common causes of such sepsis .
The research team headed by Professor Andreas Peschel and Dr. Dorothee Kretschmer has now been able to show that the body’s own immune defense against staphylococci is strengthened by giving the acetic acid salt sodium acetate, so that the body can better cope with the severe infection. In experiments with mice that were given acetate via the drinking water or an injection, the course of bacterial sepsis was significantly improved.

Our bodies fight bacterial infection using white blood cells. The most common white blood cells in the bloodstream are so-called neutrophils, which recognize, ingest and destroy pathogens. Neutrophils have various pattern recognition molecules, receptors, on their surface, to which bacteria-specific components bind and thus signal the presence of bacteria. One such component is acetate, which is formed by many bacteria, especially infectious agents such as Staphylococcus aureus and by intestinal bacteria when food is digested. Acetate is recognized by the GPR43 receptor on the neutrophils.

Acetate as an activator
“In our study, we were able to investigate in detail for the first time the effects of the binding of acetate to neutrophils. It seems to be an amplifier that wakes up the granulocytes, so to speak, and puts them on the alert, ”reports Dorothee Kretschmer. “Acetate has a regulatory effect by activating the GPR43 receptor, so that the body’s own immune response can take place adequately and specifically on several levels.” If granulocytes are already on the alert before an infection, they can react more effectively to the invading pathogens. They then move faster from the blood to the infection site, absorb more bacteria and produce so-called oxygen radicals that kill the bacteria. This led to the bacteria spreading through the bacterium during a subsequent sepsisStaphylococcus aureus were less able to multiply and distribute in the organs.

In experiments, the research team demonstrated that an acetate injection or the administration of drinking water containing acetate leads to an improved immune response in mice. “In the case of a subsequent sepsis caused by infection with staphylococci, the bacteria were killed faster and more efficiently, thus preventing a fatal outcome,” says Kretschmer. The mice recovered faster, which could be seen, among other things, from a faster weight gain. “Interestingly, we were able to observe the same effect when we administered the acetate after the onset of sepsis,” reports the first author of the study, Katja Schlatterer from the CMFI. “This also led to an improved immune response and defense against infection.” The research team believes it is conceivable that acetate could be used both preventively and for the treatment of sepsis in humans. Acetate is already being used in the clinical field, for example as an acid-base regulator in infusions that are placed when there is a loss of fluid. The tolerance in humans has thus already been proven.