Virus which infects bacteria




















That is more viruses than there are stars in the universe! Most of these ocean viruses infect bacteria [ 1 ]. Maybe all of this is new to you, but bacteria and viruses have been around for a very long time.

Bacteria have been evolving alongside viruses since the origin of life. They have been locked in a constant battle for over 3 billion years [ 2 ].

After all that time, bacteria have evolved a few tricks to defend themselves. Your body has lots of ways to keep you from getting sick or to help you get better more quickly when you do get sick. Your first line of defense is your skin and the membranes inside your body. These keep nasty bacteria and viruses away just like a wall. When you get a cut, why do you have to be careful to keep it clean? So that you do not get an infection. Sometimes though, your skin is not enough, and you do get sick.

When you get a fever, that is a sign that your body is trying to fight whatever is causing you to be sick. There are some clever ways your body can fight infection [ 3 ]. After your body fights off an infection by a virus for the first time, it can form a memory of what that virus looks like. That way, you would not get sick from that virus again. A vaccine shows your body a little bit of a dead or weakened virus, so your body can remember the virus and fight against the alive version later on.

Some viruses change over time though, so that these memories do not work forever. Have you gotten a cold or the flu more than once? That is because these viruses change quickly. Each time you get sick, it is actually a slightly different version of the cold or flu. Bacteria seem a lot simpler than us. After all, they are really tiny and only made up of a single cell. Bacteria do not have brains or other organs. Even their one cell looks much simpler than one of our own cells.

Even so, bacteria can defend themselves from viruses a lot like we do. Viruses need to attach to the outside of a cell and poke through to get inside. If the bacteria change the shape of their cell walls, this can prevent viruses from sticking to them. Then the bacteria are protected from infection. Well, some bacteria also have adaptive immunity, just like we do!

That means they can store a memory of a virus to help them protect themselves later on. Scientists only discovered this relatively recently [ 4 , 5 ]. Before, nobody thought bacteria were complex enough to have something like adaptive immunity. Nature continues to surprise scientists with new, weird stuff. The phage infection cycle seems to be simple but extremely efficient: a single phage injects its genome into a bacterial cell, switching the cells' programme in its favour so the host cell will eventually die and release about new phage particles.

Studies of bacteriophages became an essential part of biology because their omnipresence was tightly linked to bacteria. Analyses of bacteriophage genome sequences provide the opportunity to identify basic principles of genome organisation, co-evolution, as well as model and modify their genome.

This presumption is based on the fact that phages infecting certain bacteria may recognise and infect these despite their antibiotic s resistance. Indeed, exponential effects of phage growth in cells has proven very important in combating bacterial diseases.

The Caudovirales order of bacteriophages is characterised by double-stranded DNA dsDNA genomes, which can be of the size from 18 to kb in length.

Although genome sequences vary quite significantly, the virus particles of this group have a quite similar organisation: each virion has a polyhedral, predominantly icosahedral, head capsid that contains a genome. The head is bound to a tail through a connector, and the distant end of the tail is equipped with a special system for piercing a bacterial membrane.

The bacteriophage tail and its related structures are essential tools of the phage during infectivity process securing the entry of the viral nucleic acid into the host cell. Rossmann's group has been involved for many years with analysing different viruses and a significant part of their research is dedicated to the bacterial virus T4 that belongs to the Myoviridae family Ackermann, Tail contraction is an essential phase of cellular infection by these phages, resulting in pressing the central tail tube through the outer cell membrane similar to a syringe, thereby creating a channel for DNA ejection from the capsid and into the host cell Figure 1 ; Leiman et al , Bacteriophage T4.

The left panel illustrates the phage in the extended state, whereas the right panel shows the phage in the contracted state. The middle panel shows enlarged fragments of the tail both in extended and contracted states; the upper part of the middle panel demonstrates the fitting of the X-ray structure into EM map. Subunits shadowed in red show their rearrangement in the same helical strand adapted from figures kindly provided by Petr Leiman and Michael Rossmann.

Tailed dsDNA phages are characterised by their futility for crystallisation trials, although crystal structures of some individual protein components have been determined for T4 bacteriophage by the Rossmann lab. Structural studies of other phages from the Myoviridae family were hampered by variation and diversity in the amino-acid sequences among the tailed bacteriophages, making prediction of the structural organisation of phage elements unreliable.

To give you a sense of their size, if a phage were the size of the period at end of this sentence, then humans would be almost 4 miles 6 km tall! Phages are the simplest and most abundant organisms on earth. Phages are really very beautiful Figure 2 and the way they reproduce is quite interesting. A phage attaches to a bacterium and injects its DNA into the bacterial cell. The bacterium then turns into a phage factory, producing as many as new phages before it bursts, releasing the phages to attack more bacteria.

This means that phages can grow much more quickly than bacteria. In some countries, particularly in Eastern Europe, phages are actually used to treat bacterial infections. Each phage can only kill one type of bacteria, so if a doctor knows what kind of bacteria is infecting a patient, it might be possible to give the patient a phage that can infect and kill that type of bacteria.

Phages cannot infect human cells, and so they pose no threat to us. We have known for years that lots of phages are present in the gut, but we really did not know very much about them. So, we started to study them.

First, we separated the phages away from everything else in the gut, and then we sequenced them. We were amazed to learn that there are tens of thousands of different phages in the human gut. Most of them were completely unknown. Some of the gut phages are very simple and only have three genes, while others are huge and have more than genes.

If there are lots of phages present in the gut and they replicate very quickly, why do they not just wipe out all of the gut bacteria? Well, as is often the case in science, the answer is quite complicated. Sometimes the phage just cannot find its correct bacterial target in the very crowded environment of the gut.

As a result, there is a complex balance between phages and bacteria in the gut, and a stable relationship is formed. Bacteria are constantly evolving to combat phages and the phages are also rapidly evolving to overcome bacterial defenses. Why are we interested in studying phages in the gut?

Why is anyone funding labs like ours and others that are trying to understand these simple yet complex creatures? One excellent reason is that we can learn a lot of fundamental biological principles by studying phages. Quite a few Nobel prizes have been awarded to phage researchers for that very reason.



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