How To Provoke Bacterial Suicide to Fight Antibiotic Resistance

Overuse of antibiotics has escalated the emergence of antibiotic-resistant bacteria. Unfortunately, the growth of resistance has outpaced the development and discovery of new antibiotics and limited the treatment of bacterial infections.

Now, scientists are turning to a uniquely human advantage, the ability to think and reason, to solve the issue. Now, we’re tricking pathogenic microbes into killing themselves.

In April, a team of French scientists published a new kind of molecular trickery that selectively kills harmful and antibiotic-resistant bacteria without traditional antibiotics. The research, led by genomicist Rocío López-Igual and colleagues at the Pasteur Institute capitalized on mechanisms of gene regulation to trick Vibrio cholerae into producing self-destructive toxins. This approach could be adapted to target other microbes and reduce the need for antibiotics.

Antibiotic-resistant bacteria are a major threat to human health

V. cholerae, which causes cholera, encodes multiple toxins in its genome. Bacterial toxins inhibit vital processes like DNA replication or cell division. Typically, anti-toxins – that the bacteria also produce themselves –protect bacteria from poisoning themselves. Stress activates the toxins, often leading to cell death. Although exactly why bacteria maintain deadly toxin genes is still puzzling, we know that artificially activating the toxins provides a route to kill bacteria. The star of López-Igual and her colleagues’ method is a toxin that inhibits, an important bacterial enzyme. Normally, DNA gyrase relieves stress from twisted DNA strands, so preventing DNA gyrase activity causes breaks in DNA. And like in human cells, such severe DNA damage is also fatal to bacterial cells.The researchers manipulated the DNA sequences of V. cholerae to create a code for production of the toxin in specific kinds of bacteria. The specificity of bacterial gene regulation ensures that only certain bacteria can interpret this code. Bad news for the ones that can: they end up triggering their own death.