The messenger that is supposed to call the immune cells is eliminated before it goes on its way
Marit Sloin, Haaretz, Walla News!
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The bacterium group A streptococcus causes angina (inflammation of the throat) and "rosacea" in the skin, relatively minor diseases that go away on their own or with the help of antibiotics. But the same bacteria is capable of causing severe and even life-threatening infections, when it penetrates the bloodstream, muscle tissue, fat tissue or the lung. The two most serious diseases caused by streptococcus A are the "toxic shock syndrome", which causes a rapid drop in blood pressure and multisystem damage, and the "predator bacterium syndrome" which manifests itself in the rapid destruction of tissues. These diseases affect both adults and children.
In the last two decades, there has been a worldwide increase in the incidence of fatal diseases caused by Streptococcus A. Studies conducted in Israel by a team of microbiologists from the School of Medicine at the Hebrew University and the Hadassah Medical Center show that 3.7 people out of 100,000 developed the symptoms of the predatory bacteria.
In the Jerusalem area their number reaches 11 out of 100,000 (possibly due to the density of housing) and in children sick with chicken pox the incidence rises to 61 out of 100,000.
The bacterium quickly causes extensive local damage, which manifests itself in the necrosis of the soft tissues - the fat, the muscle and the membranes that surround the muscle. Death is usually caused by systemic failure resulting from the rapid spread of the bacterium, which invades the blood and travels throughout the body. When such a patient arrives at the hospital, the disease must be identified quickly and appropriate antibiotic treatment must be given and at the same time the necrotic tissue must be surgically removed. Despite this, mortality may reach about 80%.
What is special about the predatory bacteria? Does it contain special genes that make it so violent? The team of microbiologists, which includes Prof. Emmanuel Hansky from the Hebrew University School of Medicine, Dr. Alon Mozes from Hadassah Medical Center and Dr. Carlos Hidalgo-Grass from Hansky's laboratory, is trying to answer these questions.
Following infection with a bacterium, a general recruitment of immune system cells occurs in the body. When the bacterium invades the tissue, signals are sent from the tissue telling the immune system to start mobilizing. Neutrophil-type immune system cells are the first to be recruited. These cells are constantly wandering in the blood, and when they come into contact with the chemical signals secreted by the tissue, they are activated, migrate to the site of invasion of the infectious agent, swallow the bacteria and destroy them. This is the first line of defense of the immune system against most bacteria.
Usually, when examining a tissue infected with a bacterium under a microscope, a large accumulation of neutrophils is found in the area of infection. But when you look under a microscope at the tissue contaminated with the predatory bacteria, you find a very large amount of bacteria and an almost complete absence of neutrophils. The predatory bacteria therefore prevents the immune system from organizing to eliminate it, and thus it can persist in the work of killing and finally cause the death of its victim. The group of researchers wanted to check how he manages to do this.
The researchers discovered that in the genetic material of the predatory bacteria there is a site that, in a seemingly paradoxical manner, is apparently responsible for the decline in the violence of bacteria. In contrast, "most of the group A streptococcus bacteria resigned from this site," Hansky says. "Some of them lost it, in others it underwent a mutation that prevented the genes in it from being expressed, and in others you can find inactive remnants of the genes on the site."
In the last two years, the researchers collected predatory bacteria from infected human tissues, and tested this site in their genome. "We discovered that in the carnivorous bacterium this special site does exist in its entirety, but for some reason it is not active. When we investigated the site in depth, we discovered that a certain gene that is responsible for creating a peptide (a chain of amino acids) that activates the site is inactive due to a mutation. We hypothesized that if this peptide is formed, it will activate the genes on the site and thus reduce the violence of the bacteria," Hansky says.
The researchers created the peptide in the laboratory and injected it into mice, which develop the predatory bacteria syndrome similar to humans and serve as a model for the human disease. "When we injected this peptide together with the predatory bacteria into the model mice, we saw that white blood cells were recruited to the area where the bacteria were injected, the infection stopped and all the mice in the experiment survived," says Hansky. "The next question was what is the mechanism of action of the peptide and how is it related to the degree of violence of the predatory bacteria."
The research revealed that the peptide prevents the predatory bacteria from carrying out its plan. The bacterium produces a protein that breaks down one of the neutrophil recruiters, known as IL-8, which is secreted by the tissue contaminated with the bacterium. The degradation of IL-8 prevents the recruitment of neutrophils to the damaged tissue. The peptide they injected into the mice prevented the predatory bacteria from breaking down the IL-8 recruiter and thus dramatically lowered the level of violence of the bacteria. The study, which presents the survival mechanism of the predatory bacteria, is about to be published soon in the medical journal "The Lancet".
"The question of why only a minority of group A streptococci become predators remains open," Hansky says. "Although we have identified the mechanism of violence of the predatory bacteria, it is not yet clear to us why other bacteria from the same group, which have also lost the site that moderates violence, cause relatively mild diseases. It seems that With a certain combination of factors of violence that manifests itself at a certain time and in a certain place of infection. Our ability to reduce the violence of the bacteria in a model that mimics the disease in humans is the beginning of a way to develop new measures to fight a deadly infection that is difficult to control with the means available today."
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