Viruses are infectious agents so tiny that they need an electron microscope to be seen. To give you some perspective, if you think bacteria are small and invisible (which they are), viruses are 10 to 100 times smaller than bacteria. These viruses, when they come in contact with a human host, can create havoc and make their human host very sick. Now, just as there are viruses that infect and cause disease in humans, there are also viruses that infect bacteria and cause them to die! They are rightfully called phages or bacteriophages, which basically means “bacteria eaters”! It’s like one bad guy (virus) killing the other bad guy (bacteria).
How on earth did humans discover one invisible organism eating another invisible organism?
Twort, in 1915, observed that bacterial colonies sometimes just dissolved and disappeared (lysis) and that this effect continued even when the bacterial colony was passed through a bacterial filter. Since it was known that viruses are 10-100 times smaller than bacteria, and could therefore pass through bacterial filters, Twort and Felix d’Herelle coined a term for the virus that was eating the bacteria – “bacteriophage”. They are also commonly referred to as the “viruses of bacteria”.
Bacteriophage – “Viruses of bacteria” – Why are they important to humans?
Quick question… when we’re sick because of a bacterial infection, how do we attack and kill the bacteria? The simple answer is to use antibiotics prescribed by our doctor. Sometimes, it so happens that due to the frequent use of antibiotics, the bacteria develop immunity and refuse to die, so we continue to remain sick. Now, think of our unlikely hero – the bacteriophage! The primary role of a bacteriophage is to eat/kill the bad bacteria! Imagine the role a bacteriophage could play in treating human diseases! This approach to health is also referred to as phage therapy.
What is Phage Therapy?
Phage therapy is the use of viruses of bacteria to eliminate disease-causing or unwanted bacteria. Bacteriophages can kill only a certain type/strain of bacteria, unlike antibiotics, which go on a random killing spree and shoot any bacteria in sight, even those that are good for us, thus depleting our “normal flora.” Since bacteriophages are killers of only one specific bacterial host, they do not harm our good bacteria. Also, since bacteriophages need their bacterial host for survival and can only replicate in a particular bacteria, once the disease-causing bacteria cease to exist, the bacteriophages disappear as well! They don’t hang around in our body like unwanted guests. In short, bacteriophages are the logical partners for our body’s natural defense army. However, a lot of research still needs to be done to explore the option of using bacteriophages to treat human diseases and to better understand the possible drawbacks of phage therapy. There’s still time for phage therapy to replace antibiotics, and the idea has a lot of potential!
Phage-based biopreservation – Apart from humans, what else can bacteria harm? We know that food, such as fruits and vegetables, undergoes spoilage and rot over time. The culprits here are also bacteria. Now that we know bacteriophages kill bacteria, phages can be used as killers of pests (bacteria) in fruit, cheese etc., thereby acting as natural preservatives for perishable items.
Genetic research – Bacteriophages are the smallest and simplest biological entities that know how to self-replicate (make copies of themselves); this property makes them very useful for the purposes of genetic research and studies.
Structure and Morphology of Bacteriophages
Since bacteriophages are viruses, an electron microscope helps humans visualize them and observe their structure. Phages, like all viruses, have a nucleic acid core covered by a protein coat called a capsid, which in turn is composed of subunits called capsomeres. Bacteriophages commonly have a head and a tail. The tail of the bacteriophage is used to penetrate into the bacterial cell and insert viral nucleic acid into the bacteria. A good way to imagine this is being stung by a mosquito, wherein the mosquito bites us and transfers parasites into us, making us sick.
The morphology of bacteriophages tends to show one of these forms:
- Hexagonal head, a rigid tail with contractile sheath and tail fibers.
- Hexagonal head, flexible tail, no contractile sheath, may or may not have tail fibers.
- Hexagonal head, a tail shorter than the head, no contractile sheath and may or may not have tail fibers.
- Head made of large capsomeres, but no tail
- Filamentous type of phage.
Structurally, most phages possess either cubic or helical symmetry. Generally, cubic phages are regular solids or “polyhedral”, while helical phages are rod-shaped. The polyhedral phages are icosahedral in shape, which means that their capsid has 20 facets arranged in the shape of equilateral triangles. The icosahedral shape is a stable shape for the phage and allows greater space for the storage of viral nucleic acid. The nucleic acid in a bacteriophage may be either DNA or RNA, which could be double-stranded or single-stranded.
Fun facts about bacteriophages!
- Bacteriophages represent the most abundant biological form in the biosphere and outnumber bacteria by a factor of about 10 to 1!!
- Each milliliter of seawater contains approximately 107–108 phages and close to 1023 phage infections occur every second!!
- Our gut is a huge playground for these bacteria-eating viruses, as our gut is densely populated with 1013–1014 bacteria per gram of fecal matter!!
How do they replicate in such huge numbers?
Are you wondering how the hell these tiny little things can grow in so much abundance? To answer that, let’s try to understand what their life cycle is like. Generally speaking, phages can be classified into two main categories based on their lifecycle: strictly lytic phages (or virulent) and temperate phages.
The Lytic Cycle
Virulent phages can only replicate through a lytic cycle, which is characterized by the lysis (rupture) of the infected bacterial host at the end of the phage replication cycle. The steps in the process of a lytic cycle are as follows-
- Adsorption – This is a mandatory step for a bacteriophage to infect a bacterial host. Here, the tip of the bacteriophage attaches itself to certain receptors on the bacterial cell.
- Penetration – This process is carried out with the help of some phage enzymes. The tail core of the phage injects its DNA in the bacterial host cell, similar to the way a syringe injects a medicine.
- Transcription – Minutes after penetration occurs, the phage nucleic acid takes control of the bacterium and destroys the bacterium’s own genetic material, almost like a hijacking of the bacterial host by the bacteriophage. The phage DNA/RNA now starts replicating and making new baby phages using the bacterial host.
- Assembly & Release – Once these baby phages start forming, all the parts of the baby phages come together and form several new bacteriophages. In as little as 25 minutes following the initial infection, about 200 new bacteriophages are assembled and the bacterial cell bursts open and ruptures (lysis) to release these phages, which go on to find multiple other bacteria to make even more phages.
Medical aspect of the lytic cycle
Phage typing – Lytic phages usually only infect a single strain of bacteria, so bacteriophage typing can be used to identify and isolate certain strains of disease-causing bacteria, thus acting as a medical tool for diagnosis and for tracing the culprit bacteria responsible for a disease spreading in a given community.
The lysogenic cycle
Temperate phages follow a slightly different way of replicating. In this process, the phage DNA – instead of hijacking and destroying the bacterial DNA – becomes incorporated in the bacterial DNA itself and becomes a part of it. The bacterial cell continues to grow and multiply, but each time the bacterial DNA multiplies, the Bacteriophage DNA automatically multiplies and is transmitted to successive generations of the bacterial host. In this way, the phage DNA exists as part of millions of bacteria.
Medical aspect of lysogeny
Bacteria that cause disease do so by producing toxins. Some of these bacteria are capable of causing disease and releasing toxins only when they carry temperate phages. This phenomenon, where the temperate phage is able to make changes to the properties of a host bacterium, is called lysogenic conversion. Sometimes, due to certain chemicals or irradiation, these temperate phages undergo lysis and destroy the bacterial host cell, mimicking the lytic cell. These released bacteriophages are now free to infect other bacteria and thus the cycle goes on.
Bacteria harm us, and bacteriophages harm bacteria. Although we don’t have sufficient research to support the replacement of antibiotics by bacteriophages, they exhibit properties that make them very interesting to humans. They show great potential in being helpful to mankind by acting as a natural food preservative, helping in genetic research, aiding in diagnosis, and identifying certain bacteria responsible for a particular disease in humans.
- National Institutes Of Health (NIH) (Link 1)
- National Institutes Of Health (NIH) (Link 2)
- National Institutes Of Health (NIH) (Link 3)
- Book Microbiology – by Pelczar, Reid, Chan
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