On Phages — A War of Worlds
In the War of The Worlds, the breathtaking science fiction novel first released in the late 1800s, martians invade Earth, perplex scientists, and tear apart the British Army. As the Martians destroy England, the narrator runs away and hides, eventually emerging to learn that the Martians are dead and Earth seems alright considering the circumstances. War of the Worlds was a story of the unexplored, the unknown, but ultimately the understandable. It was a story about conflict in the biological world.
The story of phages is no less climactic. Phages (or bacteriophages) are bacterial viruses — hard protein vessels furnished with DNA or RNA that can penetrate membranes and force the transcriptional and translational machinery of bacterial cells to produce more viruses. For a bacterium, a phage infection can only go two ways.
The first outcome is the result of a lysogenic infection. Viruses that can exhibit this method of infection are known as ‘temperate’ phages. The death of bacteria infected by a lysogenic virus is perhaps merciful, perhaps cruelly suspenseful. Instead of being immediately destroyed, the phage integrates its code into the genome of the bacterium, which carries that code around and replicates it during cell division without translating the viral genes. The bacterium remains intact and the virus has its DNA replicated without any effort of its own. Eventually, however, under conditions that are still being studied, viruses will switch to the lytic cycle — the more brutal phage lifestyle.
The lytic refers to ‘lysis’, the bursting of cells. A bacteria infected with a lytic virus will translate viral genes into proteins, making new viruses that will escape the confines of the bacterial cell membrane by force. The lysed bacterial cell releases phages into the environment where they can attach to other hosts, and depending on the conditions, resume either the lysogenic or lytic cycles.
The ‘decision making process’ behind lysogeny is still being understood. However, recent studies on Bacillus species have shown the presence of a phage-specific peptide (encoded into the phage’s genetic material) that, when highly concentrated, inhibits lysis, causing cells to divide and multiply as they do in the lysogenic cycle.
In the laboratory, phages can be isolated using bacterial lawns grown on plates of agar (nutrient rich media). Samples from the soil, or elsewhere, thought to contain phages can be enriched and filtered, mixed with a host bacteria, and then plated and grown in an incubator. If phages are present in the sample, they’ll kill the bacteria in distinct circular regions called ‘plaques’.
Plaques also give a clue into the kind of infection the phage causes. Turbid or cloudy plaques are more than likely a sign of lysogeny, while complete clearings are a sign of lysis.
Phages are a nontrivial part of the 90% — the statistic that quantifies the number of cells in a human body that are bacterial, fungal, or otherwise not human. In fact, they are the most abundant biological particles in the biosphere and they play a crucial role micro-ecosystems and the population dynamics of prokaryotes. A recent study suggests that phages regularly cross epithelial cell layers, taking residence in the liver, kidneys, and even the brain (showcasing their ability to cross the blood brain barrier).
The fact that phages cannot infect eukaryotic cells can and has been exploited by humans. Phages are quickly becoming poster children of antibiotic resistance. Super-villains need superheroes to kill the bad guys and restore order, so a rise in “superbugs” driven by and now resistant to antibiotics, phage therapy is a natural source of fascination among microbiologists.
The idea is that phages can be engineered to kill “bad bacteria” — infections bacteria that can trudge through more traditional infection management strategies — all the while ignoring beneficial bacteria human life is reliant on.Once all of the target bacteria has been killed, phages cease to replicate and can be excreted from the body — released from their occupation and set aside to drift.
Perhaps by a combination of desperation and ambition, advancements in phage therapy has been successful in some pilot studies. Just last year, UC San Diego treated a patient near death from a multi-drug resistant infection using experimental phage therapy.
In addition to being used to treat bacterial infections, exhibiting molecular communication methods, and being found throughout the human body, phages are also used as vector for DNA cloning. Bacteriophage lambda has been used as a vehicle for DNA in studies of genetic recombination.
While their biogeography is still being studied, the abundance of phages is undeniable in environments that lack intense UV radiation, or abrasive elements. The applications of phages are incredible, but their role in microbial ecosystems — the very ecosystems that ultimately allowed for the evolution of eukaryotic life, is even more profound.
