Death / Environment / Microbiology / Science / Viruses / Worldwide

The Undead Assassins Living in Your Body: Bacteriophages!

Since I was introduced to bacteriophages, I have been fascinated by their crisp geometric structure that reminded me of the illustrations of leggy, warring aliens called “Tripods” from my childhood version of War of the Worlds by H.G. Wells. And in a way, these viruses share more in common with Well’s invaders than just their shape: they bring rampant destruction and death, but only to bacteria.

War of the Worlds, H.G. Wells, Cover Image © Abdo Publishing Group

War of the Worlds, H.G. Wells, Cover Image © Abdo Publishing Group

Bacteriophages (phages for short) are incredibly small; a single drop of water can contain trillions of them, and they can only be seen with an electron microscope. They are host-specific (meaning each phage species can only attack certain species of bacteria) – but every bacteria in the world has a phage or a set of phages capable of infecting it. Given their incredibly small size and the vast number of potential bacterial hosts, phages are the most numerous category of ‘organisms’ on Earth.

As viruses, phages lack the structure to reproduce on their own, and thus require a host. Additionally, they do not have a cellular structure like true biological organisms. Being ‘acellular’ like this poses a unique set of restrictions: phages cannot reproduce without a host, metabolize food, move chemicals across their membranes, etc. These restrictions mean phages are not considered living organisms, but are more like mini-robots.

Like Well’s Martian invaders, their physical structure is elegantly simple and highly efficient. Phages have two main parts: an icosahedral** head, also called a “capsid” (the weapon), and a tail studded with fibers (the transport). The head contains a packet of viral DNA protected by a protein shell, and the studded tail is used for landing on hosts.

Phages find their targets by recognizing specific chemical receptors on the bacterial cell wall. This recognition is entirely random and passive: phages are simply floating around in the ether of life, waiting to bump up against a potential bacterial victim. Once the victim is recognized, the phage’s tail fibers attach themselves to the cell wall. The sheath of the tail then contracts and the tail core pierces the membrane like a syringe, inserting the DNA from the phage’s head directly into the bacteria. Some phages rely on sheer mechanical force to punch their way through the bacterial wall, while others use chemical weapons (an enzyme called lysosome which can disintegrate bacterial cell walls, and is used to both enter and exit hosts). After they’ve penetrated the host, they can enter one of two types of life cycles: lytic and lysogenic.

The lytic cycle is the more ‘active’ of the two, and brings about ‘lysis’ or death of the host. In this approach, the phage’s DNA immediately hijacks the host’s cellular machinery and building blocks. It cleverly breaks down the host DNA and begins using those bits to reproduce its own viral DNA. It also commandeers the host’s machinery to produce mRna required for the bodies of new phages. These proteins self-assemble into head and tail structures and ‘reel’ in a copy of the viral DNA to form ‘daughter’ bacteriophages. To escape, the new phages apply lysosome to the inside of the cell wall until it disintegrates, ultimately killing the host and freeing themselves to resume their deadly waiting game.

Diagram of Bacteriophage. Image sourced from Wiki Commons © Adenosine

Diagram of Bacteriophage. Image sourced from Wiki Commons © Adenosine

(One of the most fascinating parts of this entire cycle is that it takes place within a timeframe for 25-35 minutes!)

The other approach, the lysogenic cycle, is much more passive. Once the phage infects a host, rather than hijacking and killing it, the phage inserts its DNA alongside the host’s. When the bacterium reproduces, the daughter bacteria surreptitiously carry a copy of the viral DNA, which lays dormant in each generation until it recognizes that the host is weakened or stressed. This growing frailty triggers the hijacking processing of the lysic cycle, once again creating new phages while killing the host.

Side note: As in all DNA processes, there is also room for error and mutation in replication and storage. Hosts can actually incorporate the viral DNA into their own and gain new functions (e.g., a bacteriophage turns the harmless Vibrio bacterial strain into Vibrio cholerae, which is the source of cholera).

Nuts and bolts aside, because they are so good at killing bacteria, phages have been explored as a treatment for bacterial infections since their discovery in the early 1900’s (by both Frederick Twort of Great Britain in 1915, and Félix d’Hérelle of Canada in 1917). As the phage has naturally evolved alongside their bacterial hosts for billions of years, ‘phage therapy’ has an extreme advantage over antibiotics, which bacterial strains can (and do!) become quickly resistant to. These advantages include: being harmless to humans, small yet effective doses, minimal side effects, etc. It has been found useful in fighting many medical issues such as cholera, anthrax, gastric fever, botulism, tularemia, bubonic plague, and even showing promise as a possible treatment for diseases like cystic fibrosis.

This brings hope that phages may help us deal with increasing issues of bacterial antibiotic resistance, and phage therapy is actually starting to become more popular globally, albeit slowly. Currently, treatments for humans are only used in Russia and Georgia (although used in the West against food poisoning bacteria, as in Listeria), as the result of a neat historical quirk:

After the discovery of phages by Twort and d’Hérelle, George Eliava of Georgia traveled to Paris where he worked with d’Hérelle. In 1923, he founded the Eliava Institute in Tbilisi, devoted to phage therapy. Unfortunately, Eliava was executed in 1937, but the Institute carried on even as the Soviet Union drew the Iron Curtain and became ideologically separated from Western medicine and their antibiotic camp which arose in the 1940’s. The Russians even used phage therapy during WWII as they had no Western antibiotics. There’s a sweet TEDx talk by the late professor Revaz Adamia on phage therapy and the Georgian connection at http://www.youtube.com/watch?v=sjH6m5VuR6I.

Hopefully, bacteriophages will continue to be studied both for their evolutionary knowledge and potential medical applications. In the meantime, they will continue happily infecting bacteria as they have for billions of years, much like H.G. Wells’ Martians plagued Earth for years, bringing death and destruction to their hosts, within your own body!

** I’m going to take a moment to nerd out right now, but if you click this link, you totally need to spend a good portion of the rest of your life on WolframAlpha. Unlike a ‘search’ engine like Google that just mines the Internet for key words and provides a list of links to pages or documents, it’s a ‘computational’ engine, meaning you can plug in any query and it will calculate and compute, through a massive database of curated data, the answer to your questions, as well provide you with a host of relevant information, formulas, etc.. Try it out. For real. Especially if you’re a student!!

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