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Intestinal cell defense mechanism against bacteria
Date:5/27/2011

FRANKFURT. Salmonella is widely prevalent in the animal kingdom. The reason we do not suffer from severe intestinal infections very often is due to our body's defence system, which manages to digest invading bacteria. This is why, generally speaking, a healthy human being will only fall ill if he consumes more than 100.000 salmonella bacteria via a contaminated food source, such as eggs or meat. An international team of researchers, led by Prof. Ivan Dikic from the Goethe University in Frankfurt has now found out how body cells recognise salmonella and render it harmless. Understanding this process at a molecular level is crucial in identifying new targets for treatment. Tropical and sub-tropical countries in particular, where various sub-species of salmonella are common, are experiencing a rapid increase in resistance to antibiotics, with children at greatest risk.

Salmonella infection begins with bacteria entering the epithelial cells of the intestinal mucosa. To prevent them multiplying there, special cell organelles, called autophagosomes are activated. These encircle the invaders and then become absorbed in other organelles lysosomes that contain certain special digestive enzymes, which break down the bacteria into their constituent parts. But how exactly do the autophagosomes recognise salmonella? Prof. Ivan Dikic and his research group at the Biochemistry Institute II have now shed light on this mechanism.

As reported in a current article in the scientific journal "Science", the salmonella are marked as 'waste material' by the molecule ubiquitin. In order for the autophagosomes to become active, the marked bacteria have to bind to another molecule LC3 on the autophagosomal membrane. Here, the protein optineurin plays a key role, linking the marked Salmonella to the autophagosmal LC3, thereby setting off a process of selective autophagy. But optineurin becomes active as a link only after being chemically modified by an en
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Contact: Prof. Ivan Dikic
ivan.dikic@biochem2.de
49-696-301-5964
Goethe University Frankfurt
Source:Eurekalert  

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