Bacteriophages’ mechanism of action unravelled

June 1, 2016. Bacteriophages are viruses that infect bacteria. A fundamental feature whose underlying mechanism had long remained unknown. Researchers at the Ecole Polytechnique Fédérale de Lausanne (EPFL) have now unravelled the details of these viruses’ bactericidal action right down to the level of the atom.

Eaters of bacteria

Viruses are often associated with deadly diseases. People tend to forget that we ourselves live with, and cooperate with, trillions of viruses. These symbiotic viruses, known as bacteriophages (or phages for short), are quite different from the species that make us ill, and much more numerous. They get their name (literally “eaters of bacteria”) from the hosts they infect, bacteria. Phages not only live inside us, they are also all around us. It is estimated that there are 10³¹ bacteriophages on Earth. That is 100 times more than the total number of stars in the universe. This makes them the most common entities on our planet.

Factory

As part of the process of infection, the phage injects its own genetic material into the bacterium. This is then incorporated into the bacterium’s genetic material, changing the host into a virus-producing factory. Eventually, the bacterium bursts open, and thousands of new phages flow out. This bactericidal effect is a complex but effective feature that is enormously important both to people and to the natural world. Bacteriophages keep the number of bacteria under control, thus preventing these unicellular organisms from swamping all other life on Earth.

A single drop of seawater contains one million bacteria and no fewer than ten million phages. One third of all the bacteria in the world’s oceans are killed by bacteriophages every day. The same thing happens in our own intestines, where phages form a sort of secondary immune system. They protect us from harmful outbreaks of the bacteria that are normally found in our bodies. These viruses are finding an increasing number of applications in science, one of which is as an alternative to antibiotics.

Syringe needle

The technology behind the phage has long been unclear. For this reason, the EPFL researchers have reconstructed a bacteriophage in detail. The result was a digital model consisting of millions of atoms. In particular, the model provides new insights into the structure of the virus’s tail. The tail consists of a hard tube, surrounded by a flexible sheath. As soon as the phage attaches itself to a bacterial cell, the sheath contracts and the tube penetrates the bacterium like the needle of a syringe. For many years, nothing was known about how this ingenious ‘piece of technology’ operated in such a simple virus. The model finally revealed the truth. The scientists found a number of cogwheel-like molecules that make it possible for this injection mechanism to function.

Future

These components, and the underlying mechanisms of action, are common to many other viruses. Some bacteria also use comparable tail-like structures to inject toxins into nearby cells. Thus the model not only provides important insights into the interactions between viruses and bacteria, but also into interactions between bacteria themselves, as well as opening the door to new drugs and treatments.

Sources
http://www.nature.com/nature/journal/v533/n7603/full/nature17971.html