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Battle of Bacteria - Fighting Antibiotic Resistance

Penicillin is arguably one of the greatest human inventions. Prior to its discovery in 1928, ear infections and strep throat were considered fatal. We no longer consider an irritated ear or a scratchy throat life-threatening, much in part to our ability to fight bacterial illnesses with antibiotics. But just as humans have adapted to the threat of bacteria, bacteria have also adapted to the threat of antibiotics. In fact, Bacteria have evolved to resist the effects of antibiotics.

An image of a amino acids linked together to form a protein.

Some of the most harmful bacteria fall under the group of Gram-negative bacteria. Gram-negative bacteria are a good example of a bacteria that has evolved to resist antibiotics. This type of bacteria has an outer layer called a cell envelope that can deactivate antibiotics or push them out of the cell through the use of resistance proteins. Proteins are long chains of amino acids that have to fold in a certain way to function properly. But if a protein loses its specific structure, it will no longer be able to perform its role. So, bacteria also contain the protein DsbA to help fold resistance proteins into the right shape to eliminate antibiotics within a cell.

With this knowledge, scientists at the University of Texas at Austin found a way to impede Gram-negative bacteria antibiotic resistance. In their experiment, the scientists took genes that code for resistance proteins and placed them in E. coli bacteria. This caused the E. coli to be unresponsive to antibiotics. Scientists also created a copy of E. coli bacteria that contained resistance proteins but no DsbA. They observed that in this bacteria, the resistance proteins were present but were not folded correctly and thus broke down. Then in the final segment of their experiment, the scientists took the first E. coli sample with resistance proteins and DsbA, but this time, they chemically blocked the DsbA protein. This caused the resistance proteins to lose their structure, and the E. coli became sensitive to antibiotics.

An image of the bacteria E. coli.

Through these experiments, scientists devised a way to attack resistance proteins in bacteria to make them vulnerable to antibiotics. Approaching the issue of resistance by modifying the bacteria itself is crucial because constantly discovering new antibiotics is challenging both scientifically and financially. In addition, scientists hope this approach of inhibiting DsbA will also be applicable to other types of bacteria. However, they have only tested inhibition in mice and with Gram-negative bacteria, so in the future, they will be looking to expand their study to humans and other groups of bacteria.