The Wonderful World of Bacteriophages

We all know that the primary types of infection are viral and bacterial, but what about a virus that infects bacteria? Enter the bacteriophage, a virus that infects bacteria.

Read on to learn all about bacteriophages, how they infect their bacterial hosts, and how they might be used to solve the problem of antibiotic resistance in the near future.

A head-tail bacteriophage. Credit: Adenosine on WIkimedia Commons

What Does a Bacteriophage Look Like?

All bacteriophages infect bacteria, but the way they’re structured can be quite different. First of all, their genomes (their genetic material) can be made up of either DNA or RNA. Their genome can also vary in size. The smallest known bacteriophage genome actually contains only twenty genes, but they can contain hundreds. That means that they can function quite simply or their functioning can be incredibly complex.

The most well-studied bacteriophages look like the image above, called the head-tail phage. But some lack a tail, while others are shaped like a long strand (called filamentous phages). Bacteriophages have adapted over time to take on the shape best suited to infect their host bacteria of choice.

In fact, bacteriophages are so diverse that there’s an entire field to exploring their diversity. Metagenomics is the study of genetic material obtained from environmental samples, letting scientists examine bacteriophages that have some environmental significance.

How Does a Bacteriophage Infect Its Host?

Just like viruses, bacteriophages must infect a host so they can carry on their lineage. Now, bacteriophages have two possible ways to infect their host. They can either undergo what is called the lytic cycle, which ultimately kills the host bacteria, or the lysogenic cycle, which does not kill the host bacteria. Some bacteriophages, like lambda bacteriophages, can even switch between the two.

A visual depiction of the first two steps of host infection by a bacteriophage. Credit: Graham Colm on Wikimedia Commons

The first two steps are the same: the bacteriophage’s tail attaches to the surface of the bacterium, and the phage then injects its genome inside. In the lytic cycle, the genome copies itself once inside the bacterium. The DNA contains instructions for the bacteria to create proteins required to form more bacteriophages, called capsids. By hijacking the bacteria’s internal machinery, it creates many new bacteriophages.

Once enough have been made, these new bacteriophages poke holes in the membrane. Water rushes in until the bacterium expands and bursts, allowing these new bacteriophages to be free. Now they can go out and repeat the process. It’s called the lytic cycle because the cell bursting open is a process known as lysis.

It’s easy to see the pros and cons of this process. One bacteriophage can use a host bacterium to create tons of copies. But this process also kills its host, meaning that if a new suitable bacterium is not located, the new bacteriophages will soon die.

To overcome this, some bacteriophages have adapted by using the lysogenic cycle. Once the bacteriophage’s genome is inside the bacteria, it integrates into the host bacterium’s genome in a process called integration, creating what is called a prophage. This contains the information required to undergo the replication cycle of the bacteriophage. And this change is permanent: once the bacterium divides, the offspring will also have the prophage integrated into their genome.

This process keeps the bacteriophage’s genome safe until it’s time for replication. When the conditions are right, the prophage will exit the bacterium’s genome. Once the prophage exits, the lytic cycle begins in order to release a new set of bacteriophages.

A visual depiction of the two cycles of bacteriophage infection. Credit: Suly12 on Wikimedia Commons

Bacteriophages in Medicine

It may surprise you to learn that bacteriophages might be the answer to antibiotic resistance. In fact, long before we learned how to make and produce antibiotics, we used bacteriophages to treat bacterial infections. And this makes a lot of sense: bacteriophages target and kill bacteria via the lytic cycle, and they don’t target human cells.

So, why did we stop using them? Well, this treatment was started in the Soviet Union, so the Cold War almost certainly played some role in our reluctance to adopt them. Additionally, a lot of the research published on the subject was in Russian, so the international community wasn’t very familiar with these publications. Finally, antibiotics were simply easier to make, store, and administer.

Russia and several Eastern European countries still use these methods today. And while some may scoff at the idea of using medical techniques derived almost 100 years ago, these just might be the answer to our antibiotic woes. And a recent study presented at ASM Microbe shows that this idea is starting to catch on in America, too.

While bacteria can adapt to resist certain bacteriophages as well, researchers believe that resistance to a bacteriophage is actually a temporary trait. This means that any resistance formed will not force genetic divergence and therefore will not be relevant after a resting period of time, nor will it generalize to all types of phages.

Bacteriophages are all around us. In fact, there are estimated to be ten million trillion trillion. That’s more than every other organism on earth (including bacteria) put together. It just goes to show that when looking for the next big thing in medicine, maybe all we need to do is look at the diverse world around us.

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