The End

It's the end of of a long but fruitful semester Unfortunately, I probably won't be posting any longer. I hope this blog shared some useful information. It was fun reading about all the current (and not so current) events and research taking place right now. Soon I hope to use this knowledge to help others get well and prevent the spread of infectious diseases. For now, thanks for reading and goodbye!

Using Viruses Against Resistant Bacteria

   by  AJC1 

Bacteriophages (phages for short) are viruses that infect bacteria, usually only a certain species or strain. In the 1920s and 1930s phages were used to combat bacterial infections before the widespread use of antibiotics. The introduction of antibiotics pushed phage therapy out of use because phages were difficult to study and manipulate and antibiotics were easier to administer and could cure numerous infections. Phage therapy is still being used in some countries in the Baltic and Eastern Europe. Modern medicine has seen vast improvements in molecular biology, genetics, and biochemistry that could make bacteriophages the successor to antibiotics and a cure for antibiotic-resistant infections.

Bacteriophages are highly specific and can be modified to only infect a pathogenic microbe. Phages by nature only attack bacteria and can be safely administered to other organisms, including humans and livestock, with very little risk. There are no side effects and the body naturally eliminates the phages.  Antibiotics are chemicals designed to damage and destroy bacteria unrestrained, whether or not the affected microbes are virulent or normal body flora. The destruction of beneficial bacteria can lead to further infections by opportunistic pathogenic bacteria and could upset homeostasis. Phages are specifically modified to target a single microbe and can be selected to only attack one strain, so virulent forms of common beneficial bacteria can be eliminated without killing normal body flora.

Bacteriophages are better on-site antimicrobial agent compared to oral or injected antibiotics. Chemicals released into the body are absorbed, spread, and eliminated. The site of an infection (inflamed wound, lymph nodes, organ, etc.) might only get a diluted compound that may not be effective. One of the reasons antibiotics are prescribed for several days to weeks is to build up a concentration that is lethal to the pathogens. Missing a dose could lower the concentration in the body and allow resistant bacteria to survive.  Parts of the body that have nothing to do with the infection also get a lethal dose and normal bacteria die. A bacteriophage grows in the target bacteria, so it concentrates where the target is concentrated. The infected area quickly becomes saturated with the virus as it infects bacteria, multiplies, lyses the cell, and attacks other targets nearby. It is an exponential growth of the virus where it is needed most, and causes the pathogen numbers to exponentially decrease. The virus is not active where targets are not present and does no harm except to the specific species or strain for which it is designed for.

Bacteriophages can be modified to enhance their specificity and prolong their effectiveness. Genetic engineering and molecular biology have made it possible to alter viruses to make them more potent and more specific. A virus or family of viruses could be altered several times to attack bacterial species within the same genus. The benefits are “custom” treatments that will target only the microbes that are causing a disease.  Bacteria can eventually develop some immunity to a virus. 

To make treatments effective, it is usually necessary to combine several viruses into a cocktail that targets one to several species in several different ways. It makes it harder for bacteria to react and become resistant, and even kills already resistant strains because multiple different phages are present. Over time, it will probably be necessary to modify the virus as bacteria start to cope with it, and in some instances phase out phages that are ineffective. However, it is not known how many times a virus can be altered, and there are hundreds of bacteriophages to use. Once the knowledge and technology are established, it would be very easy and relatively inexpensive to quickly change the cocktail, and it could be changed many, many times.

A few problems with phages are present right now. The technology and research are not at a commercial state yet, so engineering viruses is still expensive. The viruses need to be in a cocktail of several types and an adjunct to make sure the virus stays in the body long enough to kill all the target cells. The easiest and least expensive way to culture large amounts of virus now is to grow host bacteria and let the virus replicate in the host. Certain highly specific bacteriophages to highly virulent species have to be grown in the cell, which means facilities growing large quantities of dangerous organisms. Phages are made primarily from proteins, so there is a risk that it will be viewed as an antigen and could illicit an immune response such as an allergic reaction. But there is another benefit viruses can have without actually using live phages.

Bacteriophages produce a class of enzymes called lysins that digest the cell wall of bacteria and kill the cell.  Lysins are used by the virus the break down the cell wall prior to bursting the cell and releasing copies. They can lyse cells from the outside as well, even when phages are not present.  The enzymes have been isolated and research is being done to find uses for it. Lysins could be administered just like antibiotics, but they are more specific. Some lysins will only kill one species of bacteria but will not harm other species from the same genus. There are many lysins already available, and there is no indication that bacteria can build a resistance to it.

Phage Renaissance