Unmasking Pathogenic Bacteria; Protein Can Identify Camouflaged Salmonella
The highly infectious Salmonella is one smart bacterium. It camouflages itself inside human cells and slowly hijacks cellular mechanisms by secreting proteins that mimic proteins of the host cells. But sometimes the host body is able to see through its bluff when a group of proteins called interferon-induced GTPases identify the pathogens cover and expose and destroy it. The discovery was made by Prof. Petr Broz's research group at the Biozentrum of the University of Basel and will be published in the current issue of Nature magazine, according to a press release Wednesday.
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The dreaded Salmonella acts by turning the body's own defenses against it. It attacks the macrophages or white blood cells in the host body and instead of being eaten up by the bacterium-destroying macrophages, the pathogen finds a safe haven inside them. Salmonella attach themselves to the vacuoles within the cytoplasm of a macrophage, turning it into a place to safely multiply, hidden from the immune system as the macrophage is still alive. Their location is thus unknown to the body's defenses until they break out of the macrophage.
But the new study shows that the macrophages have developed a mechanism to outwit the bacterium. The interferon-induced GTPases secreted by the invaded macrophages uncovers the hiding place of the pathogen.Etienne Meunier, lead researcher explains, "They are responsible for destroying the hiding place of the pathogen and to initiate the immune response of the cell." Once the bacterium has been discovered inside the host cell, the GTPases are transported into the vacuole to destroy its membrane. Once it is destroyed the bacterium within the cytoplasm remains exposed and is recognized by the intracellular defense.
"The GTPases are the key to the hiding place of the bacteria. Once the door has been opened and the protective vacuole destroyed, there is no escape. The bacteria are immediately exposed to the defense machinery of the cell", says Meunier.
Receptors in the cell identify the pathogen, which then activate B and T lymphocytes and other special cellular enzymes to destroy the bacteria. The infected cell also undergoes apoptosis where the cell's own proteases, so-called caspases, are activated to trigger its death without harming the surrounding tissue.Salmonella causes a host of diseases including typhoid fever, food-poisoning, and paratyphoid fever. In the US. alone 40,000 cases are reported each year. Understanding the strategy it uses to invade and multiply within a host cell and the role of GTPases in its inhibition can be used to develop vaccines to counter Salmonella infections. Broz and his team now plan to further research the mechanism that goes into the detection of the pathogen inside the cells, the vacuole in the cytoplasm of the macrophages, and the transport of GTPases into the vacuole.
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