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With the growing threat of antibiotic resistance, there is a growing need for new treatment strategies for life-threatening bacterial infections. Researchers from Lund University in Sweden and the University of Copenhagen may have identified such alternative treatment for bacterial meningitis, a serious infection that can lead to sepsis. The study is published in Nature Communications.
Our immune system must appeal to several important advocates when an infection affects the central nervous system. The researchers have mapped what happens when one of them, the white blood cells called neutrophils, is involved in bacterial meningitis.
In case of infection, the neutrophils unfold in the infected area in order to capture and neutralize the bacteria. The battle is hard and neutrophils usually die, but if the bacteria are difficult to eliminate, neutrophils use other tactics.
"It's as if, frustrated, they turned in a desperate attempt to capture the bacteria they had not been able to defeat. With this approach, they capture multiple bacteria in both lattice-like structures and neutrophil extracellular cells. It works very well in many parts of the body, where NETs containing the captured bacteria can be transported in the blood and then neutralized in the liver or spleen, for example, but in the case of bacterial meningitis, these NETs get caught in the cerebrospinal space and the cleaning station is not very effective, "says Adam Linder, badociate professor at Lund University and infectious disease specialist at Skåne University Hospital.
The researchers observed, using advanced microscopy; that the cerebrospinal fluid of patients with bacterial meningitis was cloudy and covered with nodules, which proved to be NETs. However, among patients with viral meningitis, the cerebrospinal fluid was free of NET. When the captured bacteria are trapped in the cerebrospinal fluid, it harms the immune system's work of eliminating bacteria and also prevents conventional antibiotics from attacking the bacteria, says Linder.
Would it be possible to cut the nets so that the bacteria are exposed to the body's immune system, as well as to antibiotics, thus facilitating the fight against the infection? Since NETs consist mainly of DNA, the researchers studied what would happen if you imported drugs used to cut DNA, called DNase.
"We administered DNase to pneumococcus-infected rats, which caused bacterial meningitis and could indicate that the NETs had dissolved and the bacteria had disappeared." It seems that when we cut the NETs, the bacteria are Exposed to the Immune System It's easier to fight off bacteria alone.We could facilitate a significant reduction in the number of bacteria without antibiotic intervention, "said Tirthankar Mohanty, one of the researchers at the University of Ottawa. origin of the study.
Before antibiotics, the bacterial meningitis mortality rate was about 80%. With the advent of antibiotics, the death rate quickly fell to around 30%.
In the 1950s, Professor Tillett of Rockefeller University discovered mbades in the cerebrospinal fluid of patients with bacterial meningitis. Tillett discovered that these mbades could be dissolved using DNase. This effective combination with antibiotics has reduced the meningitis mortality rate from about 30% to about 20%. However, this treatment had side effects because the DNase was extracted from animals and could therefore trigger allergic side effects.
"At that time, everyone was so happy with antibiotics, they reduced the mortality by infection and we thought we had won the war against bacteria.I think we have to go back and pick up some of the research that has We may be able to learn from some of the discoveries that were later thrown into the sewers, "Linder said.
"The development of resistance in bacteria is accelerating and we need alternatives to antibiotics." The drug we use in the studies is a human-derived therapeutic biological product and already approved for They are cheap and have been tested Bacterial meningitis is a major challenge in many parts of the world, for example in India it is a leading cause of death in children, so Such a treatment strategy would bring considerable benefits, "says Mohanty.
The researchers want to set up a major international clinical study and use DNase in the treatment of patients with bacterial meningitis.
Source: University of Lund
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