Interesting Inhibitors

As patients continue to stay heavily dependent on antibiotics to treat bacterial infections, bacteria are becoming increasingly resistant to these conventional treatment approaches. Plasmids, found on the surface of yeast and other bacteria, are fragments of DNA that allow genes to be transferred between bacteria to allow large populations of bacteria to become resistant to antibiotics. These genes encode proteins that block the efficacy of the antibiotics, posing as a medical danger for patients worldwide.

Researchers at the Université de Montréal have developed a potential solution to prevent gene transfer between bacteria. This novel technique isolates TraE as the primary protein facilitating the transfer of antibiotic genes. This cytoplasmic protein plays a critical role in plasmid DNA replication, serving as an intermediary in the DNA transport process. The researchers utilized a method known as X-ray crystallography to pinpoint molecular binding sites that could potentially inhibit the function of the TraE protein. X-ray crystallography is an important method of constructing an accurate representation of the protein; its mechanism relies on the diffraction of x-ray beams to create a “lattice” pattern that depicts the binding sites and intricate structure of the protein. Using this method, the researchers are working towards finding molecules that can inhibit the expression of the protein by fitting in the binding site in place of the plasmids.

Artificial Bacterial Transformation
This image depicts the process of bacteria transformation to those that are antibiotic resistant via DNA plasmids
Image from Wikimedia Commons

After identifying the binding sites of the TraE protein, the scientists tested the efficacy of a host of chemical molecules in inhibiting the expression of the protein. The researchers began this part of the study by identifying the molecule or combination of molecules with the most affinity to the binding site. After finding one molecule that would effectively bind to the alpha-helical region of the binding site and another that would bind adjacent to another binding site of the protein, they decided to combine the two molecules for maximum affinity. The researchers also noted in further studies that a combination of two different chemical molecules at separate binding sites on the protein proved to inhibit cross-linking of the protein and decreased TraE-assisted DNA transfer by 45%, paving the way for further analysis into the inhibitory mechanisms that allow these molecules to have such a profound impact in blocking gene transfer. They also found that the structure of the protein varied between dimers which could mean that inhibitory molecules may have different effects on each dimer of the protein in their ability to block the binding site.

These results provide valuable insight into isolating the most effective molecules in inhibiting protein expression out of a massive variety of potentially effective molecules. According to Joanne Liu, international president of Doctors Without Borders, “by 2050, 50 million people will die from antibiotic resistant infections”, making this area of study essential to the future of biological research. The results of this study can prove to be beneficial beyond analysis of the specific TraE protein; researchers are currently looking to use a similar mechanism to inhibit the proteins contributing to gastric Helicobacter pylori infections that run rampant in nations lacking access to expensive medical treatments.

This recent discovery connects to the third “big idea” of AP biology, specifically the topic discussing the role of heritable information in biological processes. By studying the mechanisms by which DNA is transferred between bacterium, researchers are provided with more information regarding arising problems posed by antibiotic resistance and ways to combat this harmful phenomenon. This material also makes relevant connections with course information regarding protein expression and inhibition, as the TraE protein plays an important role in stopping the process of resistant gene transfer.

About Mr. Mohn

Biology Teacher

This entry was written by Vandita G. and tagged . Bookmark the permalink.

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