Bacteriophage: How A Forgotten Virus Can be An Asset to Combat Superbugs

What is the first word that comes to your mind after hearing the word ‘Virus’?

Disease, infection, infectious, harmful, etc. right.

What if tell you there are viruses that can cure our diseases.

You might Haven’t heard before, but there does exist such viruses, which are friendly to humans.

Just like there are god bacterias, there are good viruses.

These bacterias are known as ‘Bacteriophages’ or ‘Phages’meaning bacteria eaters.

These are good because ‘Bacteriophages’ are extreme enemies of deadly bacterias which has the potential to kill us. Believe it or not but phages are the most deadly beings on the planet.

Phages were discovered independently by two researchers Frederick William Twort at the University of London in 1915, and Félix d’Herelle who confirmed the finding and coined the term bacteriophage in 1917.

Below are some mind-boggling facts about phages-

• They are the most abundant microorganism on the planet. Much more in number than the total number of bacterias present. To give you an idea. They are everywhere, in soil, in water, in your body. Just your bare hand contains more than 10 billion phages. That’s a huge number right. The pie chart below depicts the number of phages compared to rest of the microorganism

• Phages are 100 times smaller than bacterias. Under a normal microscope, they are not visible. You need an electron microscope to see them.
• The human gut contains almost one million billion phages. Whereas just one ml seawater contains one billion phages.

The most fascinating thing is that phages do not affect humans but only bacterias. Unlike other viruses phages can be a great weapon for us to fight with deadly bacterias.

How does a phage look like?

This is how a typical phage looks like. A head, a neck and a tail depicted in the above structure. Their genetic material is contained in a prism-shaped head, surrounded by a protein capsid.

Like any other virus phages need a host cell in order to reproduce and become alive. When alone they are equivalent as dead.

How do phages kill deadly bacterias?

Phages are very specific in killing bacterias. What I mean is a particular type of phages can only kill a specific set of bacterias not all types of bacteria.

In order to kill a bacteria, phages first bind to the bind to specific receptors on the bacterial cell surface with their tail fibers and create a hole, a process which, along with attachment, is coordinated by the base plate.

Next, a rigid tube is propelled out of the sheath, puncturing a hole in the bacterial cell membrane through which they inject their genetic material (DNA or RNA, double or single-stranded).

From here, there are two ways via which phages can kill the host cell. One is known as lytic cycle, where after injecting (DNA or RNA) into the host cell, the phage genome synthesizes early proteins that break down the host DNA, allowing the phage to take control of the cellular machinery.

The phage then uses the host cell to synthesize the remaining proteins required to build new phages. During this process, the host cells gradually become weakened by phage enzymes (known as endolysin) and eventually burst. The whole process looks like the image below-

In another way, known as lysogenic cycle allows a phage to reproduce without killing its host. Following the injection of the phage DNA into the host cell, it integrates itself into the host genome, with the help of phage-encoded integrases, where it is then termed a prophage. The prophage genome is then replicated passively along with the host genome as the host cell divides. Something like shown in the below picture-

This process does not kill the bacteria directly but then under the right conditions (UV light, low nutrient conditions), the prophage can become active and come back out of the bacterial chromosome, triggering the remaining steps of the lytic cycle and kill the bacteria.

How does a phage decide whether to enter the lytic or lysogenic cycle when it infects a bacterium host cell?

One of the major factors is the number of phages infecting the host cell at once. Larger numbers of co-infecting phages make it more likely that the phages will use the lysogenic cycle.

This strategy may help prevent the phages from wiping out their bacterial hosts by toning down the attack if the phage-to-host ratio gets too high.

Because phages need a host cell to reproduce, they don’t want to run out of hosts. Thus, the tendency to flip to lysogeny at high abundance might have been favored by natural selection (explaining why phages are in such huge numbers).

But why are we suddenly interested in bacteriophages?

Although discovered first in 1917, we never paid enough attention to phages and there is a reason behind that.

In the earlier days, just a single cut in your body could have killed you. Bacterias were the culprits. We didn’t have an answer for them. People then moved their attention towards phages and successfully cured bacterial diseases by applying phages as weapons.

However, in 1928 Sir Alexander Fleming discovered penicillin and everything changed. We invented antibiotics and they were so effective against bacterias that we forgot about phages.

We became so habituated with antibiotics that we used them more and more for less and less serious causes. We lost respect for the little monsters (bacterias) and the weapon (antibiotics).

As a result, with time bacterias started to become immune against our invented weapon (antibiotics). Today there are hundreds of bacterias which are resistant towards most of our antibiotic. They are known as ‘multi drug resistant bacteria’.

Once we feared that soon there might be some bacterias that will be resistant to all our invented antibiotics and we will again go back in time, where a simple cut can kill us. Sir Alexander Fleming warned us-

“there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.“

We have already created such monsters known as ‘Superbugs‘. And believe it or not but they can wipe out human existence.

In fact, according to a survey, by 2050 superbugs could kill more humans a year than cancer. The days when a cut or cough or simple infection could kill you or your loved ones are coming back.

In such circumstances, scientists again turned their attention to forgotten tiny phages. In fact, phages are perhaps better than antibiotics to combat with bacterias.

Because antibiotics are like unguided missiles. It kills everything (good and bad bacteria) that comes within its range. But phages are very specific, they are like guided missiles.

By now, you already know how phages kill bacterias (discussed above).

In fact, there are many instances recently, where doctors have used phages to treat patients successfully.

You might be thinking, won’t bacterias develop ways of defending themselves?

They will evolve against phages too. But wait a minute, phages are also microorganisms, so they evolve too. There is a constant war going on between phages and bacterias from billions of years. Fortunately, phages won the battle almost all the time.

And even if bacterias become immune against phages someday, we will still be able to win against bacterias. It has been found that in order to become resistant to even just a few species of phages, bacteria have to give up their resistance to antibiotics. It’s like attacking the enemy with two different classes of weapons.

This has already been successfully tested patients who had no other hope left. Bacteria have no answer to the combination of phages and antibiotics.

But why don’t we hear more about phages in medical science?

Unfortunately, although there is a growing interest among scientists about phages but treatment via phages is still in an experimental state. Pharma companies are reluctant to invest in phages to a great extent. As a result, it has not become part of medical treatment. There is no official approval yet.

But things are changing, in recent years phages are getting more and more attention. Research is going on to see how safe phages are if we inject them from outside.

We better do more sound research on phages and make them a part of our medical treatment before superbug kills millions of lives all over the globe.

It might sound weird but injecting the deadliest being on the planet into the human body might save millions of lives. And who knows one day your doctor might write you a prescription for phages along with or instead of antibiotics.

An informative video on this topic-

Please, never use antibiotics mindlessly. Do remember what Sir Alexander Fleming said-

Source:

1. Technology networks
2. Khan Academy-bacteriophage
3. Phage treatment of human infections
4. Encyclopedia Britannica
5. Advantages and Limitations of Bacteriophage