Phages

by Yan Linhart

Phages are by far the most abundant organisms on earth. That fact alone provides a good enough reason to learn about them. Another reason is that they eat bacteria for a living. That is why their formal name is bacteriophages. The word Phage comes from the Greek, and has been translated as nibbler, eater or devourer, which covers some of the ways in which these viruses munch on their bacterial hosts. A third reason is their looks: if you are a fan of space travel, you can visualize a lunar module with its bulbous body and long, grasshoppery legs. That is what many phages look like, and our bodies are full of these micro-modules transporting DNA around.

Phages have one objective: to produce more copies of themselves, and one way this happens is quite spectacular. Imagine: you are looking at some healthy creature, and suddenly the creature explodes and hordes of alien modules emerge from the slime. That is what phages can do: they produce more copies of themselves by entering host cells and taking over. Then they multiply, and once their host cells burst, thousands of phages stream out and hunt other targets.

Such phage invasions followed by explosions of living bits are not science-fiction, but pretty accurate descriptions of what happens in some environments such as the deep oceans where life is dependent on these protoplasmic fireworks. Phages help provide nutrients by making bacterial cells burst. These nutrients are essential to the food pyramid in those depths where no plants live. The food provides the materials needed to grow more microbial cells, many of which are consumed by larger organisms, so the bacteria + phage combination forms an unending loop of life promoting more life. In other words they are essential drivers of life in the oceans.

Phages are also plentiful on land: we see them in all environments where their bacterial hosts are present, including our bodies. In other words, wherever we detect bacteria on or within ourselves, phages are there too, and depending on their preferences, they can nibble or devour their hosts with gusto.

What does their presence mean to us in our everyday lives? They are major players in some pretty interesting stories.

It seems that some phages, called temperate phages, are not ravenous devourers but instead live inside their hosts without killing them. The DNA of these phages can insert itself into the DNA of their hosts, and later detach from this DNA and go off on its own. These episodes of insertion followed by later detachment are the interesting part.  As is always true in nature, mistakes happen, and as a result, bits of bacterial DNA can remain attached to phage DNA, and be carried off after detachment. The next time this phage-bacterial DNA combo inserts itself into another host, some or all the bacterial DNA transported by the phage can stay behind in its new bacterial host. At this point, if you are thinking “HMMMM, I wonder if this means that information has been transferred from one bacterium to another…” Well, you are right!

Such movement of information from one bacterium to another is called horizontal gene transfer, and it is very different from the more typical vertical mode of gene transfer in which DNA is transmitted from parents to offspring. So phages can be thought of as transporters that can help their hosts become shape-shifters that adapt quickly to their changing environments. As a result, they promote very rapid evolution, and they speed up the evolution of resistance to antibiotics in some bacteria.

Phages are very focused parasites. They infect only bacteria, and individual types of phages infect only specific species or even specific strains of bacterial species. That information led the co-discoverer of phages, Felix d’Herelle to the clever idea that maybe we could use host-destroying phages as anti-bacterial agents. He had this idea about 100 years ago, and was way ahead of his time. Until recently, much of the medical world ignored his idea because antibiotics were so successful at fighting bacterial infections. However in the former Soviet Union, the concept was followed up on a very large scale, apparently with some positive results.

Now that antibiotic resistance is a standard tool in every bacterium’s survival kit, the concept of bacteriophage treatment to destroy those resistant bacteria -called phage therapy- is gaining attention. Given their specificity, phages may also have fewer side-effects, as they knock off only the disease-producers, and leave beneficial bacteria – which are often victims of antibiotics- unharmed. In addition, phages can produce enzymes which, when purified, can be used as antibacterial agents. All these good news have many people in public health fields very excited since unwanted bacterial infections are problems in both human and veterinary medicine as well as agriculture and food technology.

The fierce interactions between bacteria and phages also illustrate how evolution works: some bacteria resist phage attacks, and phages in turn develop ways to counter bacterial resistance. The latest dramatic example of this interplay is an altruistic bacterium that evolved so that phage-infected cells commit suicide to improve the survival chances of nearby bacterial cells. To counter that strategy, some of the invading phages have evolved a mechanism to prevent such suicide and a second mechanism to pass on this suicide-prevention message to other bacterial cells. Clearly, evolution is not just something that happens on faraway islands. It is a daily show all over your body. As an aside, phages are so cool that they are even catching the fancy of gamers such as Armor Games which offers a free online strategy game called Phage Wars, and model builders such as zometool.com, which bills itself as “the building toy for kids…and Nobel Prize winners” and provides a model of a phage. Even scientists known for their pretty dull prose, are writing wonderful passages about them. Some of the more lyrical ones refer to phages as friends, foes and facilitators or as movers and shakers. From these articles it is very clear that we still have a whole lot to learn about phages, and it is high time we ourselves got moving.

References

1-Hyman P, Abedon ST, Eds: Bacteriophages in Health and Disease. CABI Press Wallingford Oxfordshire U.K. 2012 296 pp.

2-Letarov A, Kulikov E: The bacteriophages in human- and animal body-associated microbial communities. Jour. Applied Microbiology 2009, 107:1-13.

3-Mills S, Shanahan F, Stanton C, Hill C, Coffey A and Ross RP: Movers and shakers: Influence of bacteriophages in shaping the mammalian gut microbiota. Landes Bioscience 2013, 4: 3 – 15.

4- Abedon ST,  Kuhl SJ,  Bob G Blasdel BG, and Martin Kutter E:

Phage treatment of human infections. Bacteriophage. 2011 Mar-Apr; 1: 66–85.

5-  Bikard D,  Marraffini LA: Innate and adaptive immunity in bacteria: mechanisms of programmed genetic variation to fight bacteriophages.Current Opinion in Immunology, 2012, 24,15–20.

6- Blower TR, Evans TJ, Przybilski
R, Fineran PC, Salmond GPC: Viral Evasion of a Bacterial Suicide System by RNA-Based Molecular Mimicry Enables Infectious Altruism. PLoS Genetics,2012 e 1003023

7-To see  a bacteriophage in action, see Bacteriophage (Hybrid Medical Animation)  on YouTube. The current issue (March 2013) of National Geographic also has images of phages and other microbes.

About the Author

Yan Linhart is a member of the Department of Ecology and Evolutionary Biology at the University of Colorado, Boulder. His primary area of interest in both teaching and research is evolution in action, and he has pursued these interests in the western USA, Costa Rica, Guatemala, Mexico, Patagonia, Wales and the Mediterranean.