Sunday, May 3, 2015

Recent Advances: Phage Therapy for Antibiotic Resistant Staph Infections

MRSA is an antibiotic resistant form of
Staphylococcus aureus, and a big problem
for hospitals. <SOURCE>

Introduction

Most of us have experienced, know someone who experienced, or have at least heard of Staph infections. As their name implies, these infections are caused by Staph (short for the bacterial genus Staphylococcus), occur on the skin, are often acquired in hospitals, and are an increasing problem as the bacteria become increasingly antibiotic resistant. One of the most famous of these bacteria is Methicillin Resistant Staphylococcus aureus (MRSA), which is resistant to many of the antibiotics normally used to treat Staph infections. As antibiotic resistance continues to be a problem, researchers and clinicians are looking to new antibiotics, as well as antibiotic alternatives. One of these alternatives is phage therapy.

We have talked about phage therapy before (click here to read more), so I will not go through it again in detail here. I will only recap by saying that phage therapy is the use of bacteriophages (bacterial viruses; phages for short) as therapeutics to treat bacterial infections. This involves administration of concentrated phages to the infection, which results in the phage infection and consequent death of those bacteria. A research article discussing phage therapy against Staph infections was recently published in PLOS ONE, and because I think phage therapy is ultra cool, I wanted to discuss it in this post. My goal for this post is to give you a brief summary of the paper, as well as some insights and perspectives about the paper and phage therapy as a whole.

The Main Points of the Paper

  • Researchers are focusing on testing a single, commercially available research phage as a therapeutic against a single MRSA strain.
  • Phage treatment of Staph infected mice resulted in reduced lesion size, but failed to reduce the bacterial counts.
  • Responses to the phage therapy (immune responses, lesion size, and bacterial counts) were dose dependent.
  • While the phage therapy limited Staph bacterial growth in artificial media culturing conditions, the therapy was not effective in human blood culture. This was the result of the blood limiting bacterial growth alone, before the phage therapy was added.
  • The selected phage therapy exhibited limited tropism, meaning it was unable to kill many strains of bacteria.
  • The phage therapy presented no significant preclinical safety concerns.

A Little More Discussion

Bacteriophages (shown in green) can infect a bacteria,
replicate inside of it, burst out killing the host, and repeat
the process. <SOURCE>
So in the end, the paper is a pretty good, standard characterization of another potential phage therapy. One important point the authors brought up was the limited tropism of their selected bacteriophage. Many phages are limited in the numbers of different bacterial strains that they can infect, which becomes a therapeutic problem. To ensure the efficacy of the therapy, the clinician would have to be absolutely sure of the bacterial strain, which is not clinically feasible. A way around this would be to create a phage cocktail instead of a single phage therapy, but this becomes a small molecule regulatory issue because every phage would still have to be tested for safety and efficacy individually before it can be added to a cocktail. The authors suggest labeling phage therapies under different regulatory guidelines, which I think is a fair point. As I mentioned a couple of weeks ago, labeling phage therapies as types of probiotics, similar to what is being done with the fecal microbiome transplants, could be a fruitful path.

I think that this tropism point is also important because it highlights the need for screening phage therapy candidates for broad tropism. A relatively small subset of phages have broad tropism, meaning they are able to target a wide variety of bacteria. Finding and using these phages as therapeutic candidates would likely minimize the tropism issues experiences by the authors of this paper, as well as the countless other researchers who experience this problem.

Another point the authors did not address, that I think is very important, is the neutralizing human or mouse immune response to the phage therapy. A significant problem in gene therapy is that the virus vector (the virus that delivers the therapy) becomes the target of an immune response, which effectively vaccinates the patient against the therapy and prevents re-administration. It seems very likely that this could occur in the phage therapy setting as well, and previous studies have indeed suggested this occurs. It would have been interesting to see whether the mice used in this study experienced such a vaccination response. This is going to have to be an important point for future researchers that investigate phage therapeutics.

ResearchBlogging.org

WORKS CITED




Pincus, N., Reckhow, J., Saleem, D., Jammeh, M., Datta, S., & Myles, I. (2015). Strain Specific Phage Treatment for Staphylococcus aureus Infection Is Influenced by Host Immunity and Site of Infection PLOS ONE, 10 (4) DOI: 10.1371/journal.pone.0124280



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