Immunology

A fragment of a protein can provide protection when antibiotics don’t work.

Bacterial infection, unresponsive to antibiotics, are a growing problem. Scientists have found new opportunities to control the development of sepsis and bacterial infections that provoke it.

According to statistics, every year, sepsis is the leading cause of death of about one million people in the United States and infants and children worldwide. As antibiotic-resistant infections, it has no effective treatment. Through a series of experiments, scientists at Boston Children’s program in the field of cellular and molecular medicine (PCMM) has revealed the final cellular events necessary to control the bacterial attack.

Studies have shown that at any sign of bacterial invasion (attacks bacteria in the body), protein complexes, called inflammasomes are activated. This activation starts the process called piropos (programmed necrotic cell death), and also delivers chemical signals, which identifitseerida, as the immune alarm. A fine line: too strong alarm can cause sepsis, which leads to fatal damage of the blood vessels and the affected organ.

“The immune system is trying his best to control the infection but if the bacteria win, the immune response can kill the patient,” explains Judy Lieberman, MD, “Most attempts to calm the immune response has not worked in sepsis treatment in clinic, as the processes that trigger it have not been understood”.
Activated inflammasome activates enzymes called caspases. Caspases cleave a molecule called gasdermin D into two parts. This cleavage releases gasdermin-active fragment known as gasdermin-D-NT. But, as this causes piropos, was not known.

Scientists have found that gasdermin-D-NT “causes” one-two punch. On the one hand, it perforeret membrane of bacteria and kills them. On the other hand “punching” holes in the membrane of the host cell triggers the immune system signals the alarm. Neighboring uninfected cells remain unharmed.

Secondly, the scientists found that gasdermin-D-NT directly kills the bacteria outside the cells, including E. coli, Staphylococcus aureus and Listeria. In the experiment this occurs for five minutes.

Understanding how gasdermin-D-NT work, can be used for the treatment of especially dangerous bacterial infections. “Because of the wide spread of antibiotic resistance, we need to think about other strategies,” says Lieberman, “”as snippet kills bacteria but does not damage uninfected cells, it is possible to imagine the introduction of the fragment directly in the affected area, especially for the treatment of localized infections involving antibiotic-resistant bacteria.”

For the blockade is too strong, an alarm can cause sepsis, Lieberman involves the development of methods for inhibiting or blocking gasdermin-D-NT, for example, using antibodies or policies of caspase enzymes.

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