Tuesday, 6 June 2017

Modified Vancomycin: Preventing Antibiotic Resistance in Bacteria

Vancomycin is an antibiotic that is prescribed to treat some potentially serious bacterial infections. For many years, it's been a powerful ally in our fight against disease. In recent times, however, it's lost some of its effectiveness. Bacteria are developing resistance to many of our current antibiotics, including vancomycin. In what could be a very significant discovery, scientists have found a way to modify the vancomycin molecule so that it becomes effective again.


Methicillin-resistant Staphylococcus aureus or MRSA is 
   being absorbed by a white blood cell in this colorized photo.
Vancomycin is used to treat MRSA. (Public domain photo)


The Importance of Antibiotics


Antibiotics are chemicals made by bacteria or fungi in order to attack other organisms. Their discovery was a wonderful time in history. Some very serious and previously fatal diseases were able to be cured by the chemicals. We are currently experiencing the reverse situation, however. As antibiotics stop working due to bacterial resistance, the spectre of untreatable diseases is reappearing.



How Do Bacteria Become Resistant to Antibiotics?


Antibiotic resistance in bacteria develops because of the genetic variability of the individuals in a species. Some individuals in a species of bacteria may contain a gene (or genes) that prevents them from being harmed by a particular antibiotic. When other members of the population are killed by the medication, the resistant ones survive. When they reproduce, they pass on the gene for resistance to some of their offspring. Over time, the population as a whole may become resistant to the antibiotic.



Vancomycin and Its Action


Vancomycin has been prescribed for over sixty years. It was discovered in 1953 in a soil sample from Borneo and is made by a bacterium named Amycolatopsis orientalis. It's prescribed as a treatment for some serious conditions that other antibiotics can no longer cure. Vancomycin may have some major side effects, however. These effects don't always occur, but if they do, they may include hearing and kidney problems.


All forms of vancomycin—natural and modified—work by interfering with the process in which bacteria produce their cell wall. The wall surrounds the cell membrane and has protective functions. Vancomycin does its job by binding to protein fragments (peptides) in the cell wall. Peptides and proteins consist of a chain of amino acids.


Unmodified vancomycin binds to two copies of an amino acid called D-alanine that end some of the peptides in bacterial cell walls. This stops the wall from being assembled and kills the bacteria. Many of the once-susceptible bacteria have now evolved to have a D-alanine paired with a D-lactic acid combination at the end of their peptides instead of a double D-alanine combination, however. Natural vancomycin can't bind with this combination and is therefore rendered ineffective.



Modified Vancomycin


A group of scientists at The Scripps Research Institute in the United States has made modifications to the vancomycin molecule to restore its effectiveness. The first modification was the creation of a form that can bind with with a D-alanine—D-lactic acid pair in a bacterium's cell wall. Other scientists created two additional modifications to the structure of the antibiotic. One prevents the cell wall from being made while the other causes the wall to burst. The Scripps team has now created vancomycin with all three modifications. This means that the altered antibiotic prevents bacteria from making their cell wall in a total of three different ways.


Resistance should be much less likely to develop when the new version of vancomycin is used. If any bacteria become resistant to one of the antibiotic's new abilities, they should be unable to resist the other two, perhaps for a long time into the future.


Animal and human trials are needed before the modified vancomycin can be prescribed by doctors. The information announced so far is both hopeful and exciting, however. We badly need either new antibiotics or old ones that work successfully again. 



References


A modified antibiotic in the fight against drug resistance from The Guardian newspaper


The creation of a more effective antibiotic from sciencemag.org