A dragon entangled in a viral icosahedral capsid

Infecting the Infectious: Viruses vs. Bacteria

Ramisa Maliha
School of Life Sciences
Independent University, Bangladesh

December 23, 2017

To be fair, bacteria are mostly our friends. The human body holds about 100 trillion commensal bacteria, that is, bacteria that do not harm us, and often benefit us. We can therefore think of them as part of our team. But not all bacteria are team players, as we are all very well aware. Disease-causing or pathogenic bacteria look to harm us in various ways, and many have even become resistant to multiple antibiotics, making treatment very difficult. But behold! Where there is life, there is predation. There is an entity on earth that outnumbers every living thing combined that most people are not even aware of: Bacteriophages (or phages, in short).

No, it’s not an insect nor some fantastic devourer of bacteria. These organisms, which are so simple that many do not label them as organisms at all, are even smaller than bacteria. Bacteriophages are viruses that infect bacteria. Bacteriophages that go through a certain kind of lifecycle end up rapidly killing the bacterial host. Because of their impressive action, bacteriophages have been employed as bacterial agents for 90 years to treat bacterial infections in humans and other species, and are prescribed to this day in places like Georgia and Russia. After all, the enemy of our enemy is our friend.

Phages on the surface of an Escherichia coli cell inject genetic material into the bacterium.© Eye of Science/Science Source

Bacteriophages first attach themselves to the surface of bacterial cells, and insert their genetic material (which can be DNA or RNA) into the bacteria by a syringe-like mechanism. The viral shell remains outside the bacterium. The injected viral genetic material utilizes the bacterium's resources and produces viral enzymes, as well as more viral genetic material. With the new viral proteins and enzymes, many new phage particles are assembled inside the host bacterium. Eventually the bacterium bursts (lyses), releasing the phage particles to infect neighboring bacteria after destroying the original host. Bacteriophages tend to be very specific to different hosts via surface binding interactions. For instance, a phage that infects Vibrio cholerae (the causative agent of cholera) would not affect Mycobacterium tuberculosis (the causative agent of tuberculosis). This property greatly accentuated their potential for use against specific pathogenic bacteria.

Frederick Twort, a bacteriologist from England is thought to be the first to suggest that phages could be used for killing bacteria in 1915. Later, Felix d'Herelle, a microbiologist at the Institute Pasteur in Paris, anticipated the use of phages to treat bacterial infection in humans, that is, phage therapy. In 1919 the first recorded phage therapy occurred when d'Herelle prescribed a mixture of phages to a 12-year-old boy with severe dysentery. At that time human trials were not as strictly regulated as we see today and the only method of knowing any side effects was for d’Herelle and his team to ingest the concoction themselves before prescribing it! According to the records, the boy’s symptoms cleared up after a single dose and he fully recovered within a few days.

Most of the results of the early research for phages to treat bacterial infections were published in non-English journals, and thus did not greatly influence research and therapy in Western Europe and the U.S. Having said that, bacteriophages were sold as a form of medication to treat a range of bacterial infections by a pharmaceutical company in the U.S called Eli Lilly as early as the 1940s. It was meant for treatment of wounds and upper respiratory infections. At that time phage therapy was not prevalent and efficient as there were no proper storage and purification methods. Also, it was not known that bacteriophages were very specific to the bacteria they attack. On top of that, the dawn of antibiotics (which were much faster and better understood) swept people off their feet and phage therapy fell out of use in most places.

Bacteriophages, as a form of therapy, have pros and cons. Most traditionally used antibiotics are broad spectrum, so along with destroying the pathogenic species of bacteria, they also destroy many beneficial bacteria making up a person’s microbiome. On the other hand, bacteriophages are very specific, which is ideal for treatment. However, bacteria can become resistant to the virus too. This problem is tackled by using phage cocktails, which incorporate many different phages targeting the same bacteria, making it very difficult for the bacteria to evolve resistance.

In the 1980s, the growing threat of antibiotic-resistant bacterial strains lead to Western scientists “re-discovering” phage therapy as a potential alternative. In the 2000s, human experiments began again, and data from the first phase I clinical trial in the U.S. was published in 2009. It is hoped that phage therapy will be an approved therapeutic option for bacterial infections throughout the world in the near future. In 2006 the Food and Drug Administration allowed the use of bacteriophages that attack strains of Listeria as a food additive on ready-to-eat meat products. This contribution of bacteriophages in the food treatment sector could be a peek into the future; replacing antibiotics and bringing an end to antibiotic-resistant supervillain bacteria such as MRSA!

Ramisa is a freshly minted second-year Microbiology student. She writes:

Biology has been the most intriguing subject to me for as long as I can remember. After being introduced to Microbiology, I found my passion in learning all about microscopic life that we interact with every day. I hope to indulge my passion by getting into the field of research and contribute to knowledge about microbes.