Last week, in Part I of this series, I reviewed the major issues associated with drug-resistant bacteria and discussed the fascinating history of the discovery and uses of bacteriophages. Bacteriophages, viruses that infect and kill bacteria, were first identified approximately 100 years ago. This week in Part II, I will discuss how a discovery made a century ago may be the solution to our current and growing problem of antibiotic-resistant bacteria.

Let’s start with a brief review of viruses. A noteworthy property of viruses is their specificity – a specific virus can only infect a specific kind of cell. For example, influenza can only infect epithelial cells in the lungs and rabies can only infect nerve cells. In a similar fashion, a bacteriophage can only infect a specific type of bacteria.

The progression of a viral infection is the same for any cell, bacterial or human. First the virus latches on to the outside of the cell. Then the cell, unaware of the really bad things that are about to happen, transports the virus across its membrane into its interior. Once inside, the virus hijacks the operations of the cell and causes many new copies of itself to be produced. Eventually the cell ruptures and dies, which allows the new copies of the virus to escape and infect new cells.

Once you understand this mechanism, the potential therapeutic value of bacteriophages is clear, and if you are a little nerdy like me, kind of exciting. If your body is infected with harmful bacteria, in theory you should be able to cure yourself by introducing a bacteria-killing virus. Further, as I will discuss below, the fact that a bacteriophage only infects its target bacteria offers some very compelling potential advantages compared to broad-spectrum antibiotics.

Production of bacteriophage preparations is not difficult. Let’s say you want to make a solution of bacteriophages that infect E. coli bacteria. You start by obtaining a population of E. coli and growing them in water. It’s a near guarantee that some of the E. coli that you started with were infected with bacteriophages. As you keep the E. coli confined in your production vessel, the viral infection will spread. As this happens, E. coli cells will begin rupturing and releasing bacteriophages into the water. You can collect some of the bactieriophages by extracting some of the water through a filter with holes big enough to let the viruses through but too small to let bacteria cells follow along.(1) Now you can incorporate the bacteriophages you collected into a syrup, pill, suppository, or cream as a possible medical treatment.

As I discussed last week, during the 1920s both bacteriophages and antibiotics were being developed as potential cures for bacterial infections.(2) In the 1930s, for a number of reasons, not all of them valid, bacteriophage development stopped in the United States and Western Europe. In stark contrast, industrial-scale antibiotic production exploded after World War II, and the resulting reduction of deaths due to simple bacterial infections, at least in the developed world, was nigh-on miraculous. At about the same time, farmers observed that feeding small doses of antibiotics to livestock resulted in larger animals and faster growth rates. In response to the introduction of antibiotics in both medicine and farming, the bacteria adapted quickly. For example, staphylococcus began showing resistance to penicillin only three years after the introduction of this famous medicine. Today, only seven decades later, multiple types of bacterial have developed resistance to a broad array of antibiotics.

I started writing an additional segment in this series devoted to explaining how bacteria develop resistance to antibiotics but not bacteriophages. Frankly, even to me, it was a bit of a dry read. So rather than writing a complete column on the topic, let me provide this brief overview. Think of an antibiotic as being a poison introduced to the bacteria population. Even though the bacteria are all the same species, they are not genetically identical. As such, some of the bacteria are better equipped to survive the poison and live on to become the Adam and Eve of the next generation. Over the course of generations – and a generation in the bacterial world is not long – the gene pool continues to shift towards drug-resistant individuals and the antibiotic is no longer effective.

The potential dynamics for bacteria to develop resistance to phages is much different. Consider that bacteria and the viruses that infect them have co-evolved for hundreds of millions of years. Therefore, as an example, if cholera bacteria were going to develop resistance to the viruses that infect them, they would have done so already. As a result, if bacteriophages were to enter wide use in treating bacterial infections, it is unlikely that phage-resistant bacteria would arise.

In addition to not causing bacteria to become drug resistant, phages enjoy another noteworthy potential advantage over antibiotics: their specificity. When you take an antibiotic, it tends to kill a wide range of bacteria in your body, not just the one causing you problems. Since human health is dependent on maintaining the proper balance of beneficial bacteria, this can be quite problematic. For example, as I discussed in Bacteria and Obesity, a Surprising Link and Perils of a Hyper-Hygienic Existence, overuse of antibiotics can cause long-term weight gain as well as increased susceptibility to infection by pathogenic bacteria. Bacteriophages only kill their target bacteria, thereby avoiding these types of collateral damage.

Renewed interest in bacteriophages in the U.S. has already led to several approved uses in food safety. Over the past several years, it has become commonplace to hear about produce that is contaminated by bacteria such as E. coli or listeria.(3) Spraying a solution of the appropriate phages on the surface of contaminated foods is a very effective way of killing the bacteria. I anticipate that this practice will grow dramatically in coming years.

As of 2015, there are no approved human therapeutic uses for bacteriophages outside of the former U.S.S.R. But their introduction is only a matter of time. There are many potential therapies being developed, but it takes several years for a new drug or therapy to receive FDA approval. I am often accused by readers of being too pessimistic about the future. In contrast, I am quite optimistic that renewed interest in bacteriophages will result in dramatic improvements in human health around the globe. Time will tell.

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1. This filtration is a fairly simple task, since viruses are around 50 times smaller in size than a typical bacteria cell.

2. There was tremendous interest in treatments for bacterial infections in the years following World War I. As had been the case for warfare throughout the ages, more soldiers died from infections than battle during the war. Furthermore, the medical community was beginning to understand that most of the people who died from the Spanish Influenza of 1919 did not succumb to the initial viral infection, but from a secondary bacterial infection in their weakened lungs.

3. Most bacterial contamination of fruits and vegetables occurs during transportation, when a truck which had recently transported animals has been insufficiently sanitized. The phage treatments for the produce could also find use in truck decontamination.