Swiss scientists described a molecular mechanism that allows tularemia pathogens to prevent their deaths within the immune response.
An important tool for the effect of bacteria on other microorganisms are secretion systems - structures that make it possible to violate the integrity of a foreign cell due to special proteins or supramolecular complexes. For the first time such mechanisms were described about 20 years ago, and until recently they were divided into five types (from T1SS to T5SS), differing in complexity and composition. In the 2000s, biologists came to the conclusion that there is a type IV secretion system. It was found in a quarter of Gram-negative bacteria, the genome of which was completely sequenced. Until now, the most complete work of T6SS has been studied using the example of cholera vibrio (Vibrio cholerae).
The secretion system of type IV is a "harpoon": when it is thrown out of the cover, it pierces the membrane of another microorganism and delivers toxins to the cytoplasm. It is known that a large number of proteins are involved in the work of the complex, but before it is used it is assembled promptly, and after that it is disassembled into separate components. V. cholerae uses T6SS for hunting bacteria and infection of host cells. In a new article, researchers at the University of Basel examined T6SS in Gram-negative bacteria Francisella tularensis, a pathogen of tularemia. Tularemia is a plague-like disease, the carriers of which are hare, hamster and blood-sucking arthropods.
A distinctive feature of F. tularensis is the ability to multiply in the cytoplasm of macrophages - the cells of the first line of immune defense. After macrophage capture, the pathogen is placed in the endosome and then into the digestive vacuole. However, F. tularensis can return from the endosome to the cytoplasm. At the same time, the genome of the bacterium contains islands of pathogenicity - loci that are characteristic of virulent microorganisms, which are capable of interspecific or horizontal intraspecific transmission. Sequencing of these sites has shown that they also include encoded T6SS, and its composition differs from those described earlier. Now scientists have clarified the features of the secretion system of type IV F. tularensis.
According to the results, the release of bacteria from the endosome is mediated by T6SS - this was confirmed by the deletion of two species-specific genes, which resulted in F. tularensis being unable to return to the cytoplasm of the macrophage. In addition, the researchers found that the pathogen collects a "harpoon" at the ends of the rod-shaped cell - probably, it allows to design a complex of greater length to increase the volume of delivered toxins. At the same time, the protein providing the F. tularensis energy system was comparable to the V. cholerae protein. Scientists note that, despite clarifying the role of T6SS, the mechanism of dissolution of the membrane of immune cells requires further study.
The article is published in the journal Nature Communications.