A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial¹ pathogen Salmonella within the cells. The so called interferon-induced GTPases reveal and eliminate the bacterium²'s camouflage³（伪装，掩饰） in the cell, enabling the cell to recognize the pathogen and to render it innocuous（无害的）. The findings are published in the current issue of the science magazine Nature. Bacteria have developed countless⁴ strategies to hide themselves in order to evade⁵ attack by the immune system. In the body, Salmonella bacteria use macrophages as host cells to ensure their survival and to be able to spread within the body. Their survival strategy is to nestle into a vacuole（液泡） within the cytoplasm of a macrophage, hiding there and multiplying. While they are hidden there, the immune cells cannot detect the bacteria and fight them.

 

Exposure: GTPases destroy Salmonella's hideout

 

The macrophages, in which the Salmonella hide, however, have also developed a strategy to unmask the disguise of the bacterium and uncover its hiding place. Prof. Petr Broz's research group at the Biozentrum of the University of Basel has discovered a protein family called interferon-induced GTPases in host cells invaded by Salmonella. "They are responsible for destroying the hiding place of the pathogen and to initiate⁶ the immune response of the cell," explains Etienne Meunier, first author of the publication.

 

Destruction: Kick-off for attacking the bacteria 

 

Once the hiding place has been discovered, GTPases are transported to the vacuole and destabilize its membrane⁷. The bacteria are left behind unprotected in the cytoplasm where their surface molecules⁸ are easily recognized by the intracellular defense¹⁰. "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 machinery¹¹ of the cell," says Meunier. Receptors in the cell identify the pathogen, which then activate¹² special cellular⁹ enzymes¹³ to destroy the bacteria. In addition, the cells own proteases, so-called caspases, are activated¹⁴ and trigger cell death of the infected host cell.

 

Salmonella still remain a feared pathogenic agent, as they can cause life threatening diarrheal（腹泻的） disease. The findings of Broz and his team enable the better understanding of the strategies of the immune cells and to perhaps model this in the future. The deeper understanding of the immune response of our cells also paves the way for new approaches in using drugs to support the body's fight against pathogens. In order to further elucidate¹⁵ the mechanisms¹⁶ of the immune response to Salmonella infections, the research team plans to investigate how cells detect the hiding place of the bacteria, the vacuole in the cytoplasm（细胞质） of the macrophages, and what initiates¹⁷ the recruitment of GTPases to the vacuole.

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