The Other Antibiotic: Viruses

Whether the name is spread by the 5 o’clock evening news, the National Institutes of Health website, or a box that you may have to check when registering as a new patient at a healthcare facility, methicillin-resistant Staphylococcus aureus(MRSA) is quite a topic of interest in public health. Wait, what is methi-huh-Staphylo-wha?

You’ve probably heard of the dangers regarding MRSA, but the name simply refers to the fact that bacteria can develop resistance to antibiotics. This can render modern treatment options ineffective, but pharmaceutical companies have made more than one compound to kill bacteria; the real issue arises when the bacterial strains can withstand several kinds of the most readily-available antibiotics. MRSA is one of these so-called “superbugs.”

For a quick lesson on antibiotic resistance, click here!

You don’t have to be in the healthcare industry to take an interest in antibiotic resistance; it can affect your fantasy football drafts, too. Daniel Fells, NFL Giants’ tight end, battled MRSA this October and had to undergo several surgeries. It is yet to be seen if the pathogen has even worse health consequences for the formerly-healthy football player.[1]

Not only is MRSA especially concerning to healthcare facilities such as hospitals, where there is a large population with compromised immune systems and high antibiotic use, but it can also breed in places where skin-to-skin contact is typical, such as athletic facilities. MRSA outbreaks have hit several NFL teams in recent years. The severity of Fells’ MRSA infection may have been worsened by his profession, but it is not the only superbug to be concerned about. Other antibiotic-resistant bacterial strains have been emerging.[2]

Fight fire with fire

For all of Western medicine’s advances, we’re still using fixed molecules – antibiotic compounds – as our means to deter ever-changing bacteria.  However, nature has been around longer and can adapt to fight the microbes more rapidly. An alternative to constantly synthesizing new antibiotics is to use something that evolves with the pathogen—this has already been identified.

Bacteriophage 1 Trac 2015
Figure 2. TEM image of a single bacteriophage isolated from sewage.

About a century ago, when antibiotics had not yet become the therapy of choice, there was an interest in eliminating target bacteria with specified viruses called bacteriophages (or for short, phages). Phage therapy, administering these viruses to bacterial infections, still had a long way to go before researchers understood how it worked, so some treatment results were inconsistent.[3]As such, the viruses were abandoned by most Western scientists in favor of newly-discovered antibiotics, but research continued notably in Eastern Europe and the former Soviet Union.[4]

There, bacteriophages have not only continued to be studied, but also be used in clinical treatments for 90 years.[3] According to these trials, phage therapy had stunning results. Once ingested, phages target only their specified bacterial strain as opposed to broad-spectrum antibiotics that could disrupt non-pathogenic microbes in the body. They then lyse, or cut, the bacteria to kill them. Phages replicate as long as their prey is present; they can then limit replication as the bacteria are eradicated and be gradually excreted by the body when no longer needed.[5]

Moreover, no documented allergic reactions have been observed. This makes sense because phages are one of the most abundant things in the environment, so they are eaten by humans all the time. These seemingly-miracle studies hold little credibility in the United States, though, due to a lack of certain Western procedural standards when they were performed by foreign researchers.[6]

Where are they now?

It is highly unlikely that patients in the U.S. suffering from a superbug infection, such as MRSA, will be treated with phages anytime soon. Much of the research conducted in Eastern Europe and the countries of the former Soviet Union – while extensive – does not meet the criteria for clinical testing in Western countries where protocols such as control groups and double-blind studies are necessary. Despite the Eastern and Western medicine divide, the growing discussions of antibiotic resistance have led to whatEnvironmental Health Perspectives calls a “phage renaissance.”[3]Western researchers have begun performing experiments with bacteriophages once again. One of these scholars, Eric Trac, is working with them at the Stanford University School of Medicine.

“We went to the Palo Alto sewage,” said Trac, “almost anywhere there are bacteria, there are bacteriophages.” He was able to isolate bacteriophages from the sewer samples. Three months into his research, Trac has been sequencing the phage genomes and modeling the emergence of bacterial resistance.

Bacteriophage 3 Trac 2015
Figure 3. Eric Trac is taking a year off from his studies at the Stanford University School of Medicine to pursue bacteriophage research as a Howard Hughes Medical Institute fellow.

A drawback of the specific targeting exhibited by bacteriophages is the narrow bacteria host range, but this can be countered by using multiple phages at once to eliminate the bacteria (called a “cocktail”).[5] “It would be nice to develop a way to manipulate the host range,” Trac noted.

He suggested that phage therapy cocktails could aid treatment of Clostridium difficile (C.diff) infections where patients have a strain of bacteria that is resistant to antibiotics. Progress in Western medicine is being made: a bacteriophage cocktail was used in the United States for a phase 1 clinical trial in 2008 and was proven to be safe.[3] Phages are also currently approved by the FDA for use in food production.[7]Trac thinks that there will be a greater interest in the private sector and academia as our understanding of bacteriophages increases and antibiotic resistance becomes a greater problem.

In the early days of investigation, phage therapy results were unreliable, but over the years they have been claimed to cure a myriad of illnesses including dysentery and bubonic plague. It is also important to note that they could have the potential to protect against meningitis and zoonotic diseases.[7]

There are some concerns about bacteriophages interacting with bacterial genes to cause illness or lysing bacterial cells that release toxins. Regardless of whether they are used therapeutically, though, bacteriophages are providing researchers with never-before-seen genes.[4] With available gene sequencing technologies, phage genetic information could even be used to lyse bacteria in place of the phages themselves.[3]

Phage therapies were once considered a viable treatment of bacterial infections prior to antibiotics, even with companies in the United States.[6] Trac looked to local sewage to isolate phages; other researchers who look to the environment are also continually finding new bacteriophages.[4] Perhaps they will give us insight into how certain diseases occur or how bacteria evolve.

Phages are now more important than ever as pathogenic bacteria develop resistance to even the toughest antibiotic compounds. Researchers like Trac are needed to test phage efficacy and understand how they work. They might rekindle Western medicine’s interest with bacteriophages and possibly use them as an alternative to antibiotics.

Bacteriophages have the potential to be used in medical therapies, water treatment, and food production—anywhere there is a need to remove bacteria. However, one obstacle in continuing research, particularly clinical trials, is that microbes tend to be synonymous with pathogens. This is not the case. Researchers have apprehensions that the general public will hear “viruses” and become disenchanted with the beneficial uses.[3] Yet bacteriophages are at a fascinating intersection of ecology, genomics, and microbiology. Further studies could change how we combat bacteria, especially those superbugs that threaten to harm even the healthiest people we know.

 

References

  1. Rapoport, I. (2015, October 11). MRSA infection leaves Giants’ Daniel Fells in dire situation. Retrieved fromhttp://www.nfl.com/news/story/0ap3000000553694/article/mrsa-infection-leaves-giants-daniel-fells-in-dire-situation
  2. Thompson, D. (2015). NFL player’s MRSA infection ‘extremely unusual.’ HealthDay. Retrieved fromhttp://consumer.healthday.com/infectious-disease-information-21/misc-infections-news-411/nfl-mrsa-704191.html
  3. Potera, C. (2013). Phage renaissance: New hope against antibiotic resistance. Environmental Health Perspectives121(2), a48–a53. http://doi.org/10.1289/ehp.121-a48
  4. Travis, J. (2003). All the world’s a phage. Science News, 164(2), 26-28. Retrieved from http://www.jstor.org/stable/3982016
  5. Loc-Carrillo, C., & Abedon, S. T. (2011). Pros and cons of phage therapy. Bacteriophage1(2), 111–114.http://doi.org/10.4161/bact.1.2.14590
  6. Sulakvelidze, A., Alavidze, Z., & Morris, J. G. (2001). Bacteriophage Therapy. Antimicrobial Agents and Chemotherapy45(3), 649–659.http://doi.org/10.1128/AAC.45.3.649-659.2001
  7. Atterbury, R. J. (2009). Bacteriophage biocontrol in animals and meat products. Microbial Biotechnology2(6), 601–612.http://doi.org/10.1111/j.1751-7915.2009.00089.x

 

Trac, E. (2015, October 29). Bacteriophage research [Personal interview].

Figures 1-3 (article cover image, single bacteriophage, and researcher photo) are courtesy of Eric Trac at the Stanford University School of Medicine.

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