Wednesday, July 24, 2013

Bacteriophage

HISTORY
     It has been known for centuries that river water could sometimes combat diseases such as leprosy. In addition, sea water, we now know, has the highest concentration of bacteriophages. In 1915, Frederick Twort discovered the bacteriophage, although he did not yet know what it was. In 1917, Félix d'Hérelle independently discovered the bacteriophage. He was the one who first understood that the virus was killing the bacterium, and he had the honor of coining the term “bacteriophage.” It was used in the U.S. in the 1940s, but was more common in countries like Georgia. Phage (short for bacteriophage) treatment has been used in Eastern Europe for decades. It was used in the U.S.S.R. in the military, but there were no official studies done, so it has not caught on as quickly in the U.S. Unfortunately, during the 1930s and 1940s in the U.S., bacteriophages were not always studied or used properly, and they fell out of favor. (Sometimes, patients were treated with a phage, but phages are very specific to the type of bacterium they kill, so sometimes the phage did no good.) Today, in the U.S., there is only one place where physicians use bacteriophages. In Georgia and Poland, the treatment is more common.

GENERAL INFORMATION 


Structure of myovirus bacteriophage
(Credit: https://en.wikipedia.org/wiki/Bacteriophage)
     Phages are made of proteins which keep in the DNA or RNA. They can have anywhere from four to several hundred genes. The estimated number of bacteriophages is 10³º up to 10³². They are everywhere: on our skin, in out gut, and in our food, to name a few places. Bacteriophages kill bacteria by making a hole in them. Some phages do this by using a protein spike with an iron atom for a tip. This allows the phage to literally bore into the bacterium. Then, it releases its DNA into the bacterium so that the bacterium is forced to make more phages. Eventually, the bacterium bursts, releasing all the new phages.



    

     Mucus is made up of many mucins which, in turn, are made up of glycan sugars. It is to these sugars that the phages stick. In animals, phages are concentrated four times more densely in the mucus than elsewhere. Thus, the phages help to keep bacteria out in the first place.

 
On the left, bacteriophages attacking a bacterium (electron microscope).
On the right, computer generated model. 
(Credit: Adapted from J. Liu et al., Virology, 417 (1 September 2011), (http://news.sciencemag.org/sciencenow/2012/02/bacteria-killing-viruses-wield-a.html?ref=hp )

USES
     Currently, scientists are re-engineering bacteriophages to produce proteins that help antibiotics perform better.  The protein shuts off the bacterium’s ability to repair its DNA.  Normally, antibiotics damage DNA, but the bacterium can repair it. The bacteriophage used in this study does not kill the bacterium, only lames it. Therefore, the bacterium is less likely to become resistant to the phage. Currently, phage treatment is being used for food and veterinary processes. LND102 is a medication made of six bacteriophages which kill a specific type of bacterium which leads to food poisoning. (This bacterium kills one quarter of those who get it). LND102 is used in food to decrease the amount of people who get poisoned. Another company is developing patches to put on cuts or infected wounds which contain bacteriophages. It is biodegradable, and, as it decomposes, it releases the phages into the cut, so they can kill bacteria. A U.K. company is developing a treatment for ear infections using bacteriophages. In the future, bacteriophages may be used for treating human skin diseases, livestock (so less antibiotics go into the animal and eventually into us), and water. Scientists are looking at the possibility of creating synthetic phages to combat different types of bacteria. It may be possible, with the development of synthetic phages, to change the type of phage given to the bacterium so resistance does not develop.
                                                        
OUTLOOK
     Bacteriophages seem to be the solution to all our infectious disease problems. Although most phages are beneficial to us, some are not. The phage works by blowing up the bacterium. Some phages have toxins and specific genes which are harmful to us. When they bore into the bacterium, they, like all other phages, exchange the DNA in the bacterium. They also release the toxins which makes it more likely that both the bacterium and the phage will survive. When the right phage binds to the bacterium Streptococcus pyogens, the infected individual will contract scarlet fever. I think that there needs to be a lot more testing done before the phage is proclaimed to be so wonderful.  
     On the other hand, there are a lot of possibilities for the phage. It naturally harms and/or kills the bacterium (usually), and it mutates along with the bacterium. The main problem with antibiotics is that they are expensive, take a long time to develop, and quickly become ineffective against “super-bugs.” It appears that it is harder for bacteria to become resistant to phages, and, since they occur naturally, expenses and time may be saved in development. In the end, we will just have to wait and see. 



Bacteriophages bombarding bacteria (electron micrograph)
                                                                                  
SOURCES   
http://www.npr.org/templates/story/story.php?storyId=101547330
http://www.npr.org/templates/story/story.php?storyId=89380684
http://news.sciencemag.org/sciencenow/2012/02/bacteria-killing-viruses-wield-a.html?ref=hp
http://www.nature.com/news/viruses-in-the-gut-protect-from-infection-1.13023
https://en.wikipedia.org/wiki/Bacteriophage
http://www.sciencedaily.com/releases/2012/09/120928085348.htm    

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