Bacteria can be attacked by viruses known as bacteriophages. The vast majority of phages are composed of a capsid, which contains the genetic material, and a tail, which recognizes the host. When the tail of the phage recognizes a bacterium, the capsid opens and releases the viral DNA that passes through the interior of the tail tube and is then injected into its target. But how do the tail and the capsid communicate with each other? By combining electron cryomicroscopy and crystallography, IBS researchers have answered this question by determining the structure of the tail tube.
The scientists are interested in the molecular mechanisms that allow phages to inject their genetic material into the bacterial cytoplasm after the specific recognition of their host. In particular, they work on the T5 phage, which has a long, flexible, non-contractile tail, and which attacks the bacterium Escherichia coli. They initially determined by X-ray crystallography the atomic structure of the major tail protein, pb6, at 2.2 Å resolution. This work shows that there is a structural homology between phage tail proteins and bacterial molecular syringes, indicating their common origin.
Next, they determined the structure of the phage tail tube at 6 Å resolution, before and after host recognition, by electron cryomicroscopy. They were able to show, contrary to the mechanism proposed so far, that the host recognition information is not propagated to the capsid by the walls of the tail tube! Indeed, the two structures are identical at the resolution of study. The researchers propose that this function is provided by the pb2 protein; inserted inside the tube, this protein serves as a scaffold for the polymerization of the major tail protein and thus determines its length. This protein should be folded into a meta-stable state within the tail: the interaction with the host could induce changes in the structure of the tail extremity, destabilizing the vernier protein that would then be expelled. This could be the signal for the capsid to open and release the viral DNA. In view of the great structural conservation of major tail proteins, the authors propose that this mechanism should be common to all long-tailed phages, which represent no less than 86% of all phages.
Could phages take over from antibiotics?
Why not use phages to fight bacterial infections? Specific and self-replicating, they are the natural enemy of bacteria. This idea is not new: phagotherapy was created in France in 1919 at the Necker hospital to treat children suffering from bacillary dysentery. This method also proved to be successful in treating cases of the plague in Egypt in 1925, as well as a cholera outbreak in India in 1926 [1]. These successes had such an effect that they lead to a globalization of phagotherapy. Everything then stopped after two successive events: the discovery of penicillin by Alexander Fleming in 1928, and the Second World War, which generated huge needs for anti-infectious treatments. A priori, antibiotics appear to be easier to make, as well as more stable and easier to use. Although phagotherapy has now disappeared in the west (apart from the countries of former Eastern Europe), it is now finding a new lease on life following the development of antibiotic-resistant bacteria. Hence the importance of reviving research on phages.
[1] Annals of Burns and Fire Disasters - vol. XXVIII - n. 1 - March 2015